This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, K. Articles by Shi, Y. E. Search for Related Content PubMed PubMed Citation Articles by Wu, K. Articles by Shi, Y. E.

Stage-specific Expression of Breast Cancer-specific Gene -Synuclein¹

Departments of Surgery [K. W., Z. W., H. Q., Y. Z.] and Pathology [X. W.], XinHua Hospital affiliated with Shanghai Second Medical University; Institute of Biochemistry and Cell Biology, Chinese Academy of Science, Shanghai, China [Q. T., G. L., X. D.]; and Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, New York 11040 [Y. J., Y. E. S.]

	Abstract

Top Abstract Introduction Materials and Methods Results Discussion References

 
-Synuclein (SNCG), also referred as breast cancer-specific gene 1, is the third member of a neuronal protein family synuclein. SNCG is highly expressed in human-infiltrating breast carcinomas but not expressed in normal or benign breast tissues. To evaluate the clinical relevance of SNCG expression in breast cancer progression and its correlation with clinical parameters, we analyzed SNCG expression in 79 clinical breast specimens from primary breast cancer, hyperplasia, and fibroadenoma patients by reverse transcription-PCR. The status of estrogen receptor, progesterone receptor, proliferating cell nuclear antigen, and C-erBb2 was also analyzed by immunohistochemistry. Overall SNCG mRNA expression was detectable in 38.8% of breast cancers. However, 79% of stage III/IV breast cancers were positive for SNCG expression, whereas only 15% of stage I/II breast cancers were positive for SNCG expression. In contrast, the expression of SNCG was undetectable in all benign breast lesions. The expression of SNCG was strongly correlated to the stage of breast cancer (P = 0.000). This study suggests that the expression of SNCG is stage specific for breast cancer. SNCG is expected to be a useful marker for breast cancer progression and a potential target for breast cancer treatment.

	Introduction

Top Abstract Introduction Materials and Methods Results Discussion References

 
Using the differential cDNA sequencing (1, 2, 3) , we undertook a search for isolation of differentially expressed genes in the cDNA libraries from normal breast and breast carcinoma. Of many putative differentially expressed genes, a breast cancer-specific gene, BCSG1,³ was identified as a putative breast cancer marker (1) . This gene was highly expressed in the advanced breast cancers cDNA library but scarce in a normal breast cDNA library. BCSG1 is not homologous to any other known growth factors or oncogenes. Rather, there is extensive sequence homology to the neural protein synuclein. Subsequent to the isolation of BCSG1, SNCG (4) and persyn (5) were independently cloned from a brain genomic library and a brain cDNA library. The sequences of these two brain proteins were found to be identical to BCSG1. Thus, BCSG1 is now also named as SNCG or persyn and is considered to be the third member of the synuclein family (6) .

Synucleins are a family of small proteins consisting of three known members, SNCA, SNCB, and SNCG. The previously identified BCSG1 shares 54 and 56% amino acid sequence identity with SNCA and SNCB, respectively. The NH₂-terminal halves of SNCA, SNCB, and SNCG are highly conserved. However, although the residues near the COOH terminus of SNCA are similar to those of SNCB, those of SNCG diverge greatly from the SNCA counterpart (7) . Although they are homologous, each synuclein is encoded by a different gene on chromosomes 4q21.3-q22 (SNCA), 5q35 (SNCB), and 10q23 (SNCG; Ref. 8 ). Synucleins are predominantly present in brain and thought to be involved in neuronal plasticity and the formation of depositions in brain tissues (6) . Synucleins has been specifically implicated in neurodegenerative diseases such as AD and PD. Mutations in SNCA is genetically linked to several independent familial cases of PD (9) . More importantly, wild type of SNCA is the major component of Lewy bodies in sporadic PD and in a subtype of AD known as Lewy body variant AD (10 , 11) . SNCA peptide known as nonamyloid component of plaques has been implicated in amyloidogenesis in AD (12 , 13) . SNCB and SNCG have also been recognized to play a role in the pathogenesis of PD and Lewy bodies cases (14 , 15) .

Although synucleins have been specifically implicated in neurodegenerative diseases and serve as a hallmark for AD and PD, studies indicate a potential role of synucleins, particularly SNCG, in the pathogenesis of steroid-responsive tumors of breast and ovary (1 , 4 , 16, 17, 18, 19, 20) . Identified as a breast cancer-specific gene, we first demonstrated by in situ hybridization that SNCG was undetectable in normal or benign breast lesions, partially expressed in DCIS, and was expressed at a high level in advanced infiltrating breast cancer (1) . Others have also demonstrated the similar findings in breast and ovary cancer (4 , 18) . In this study, we used RT-PCR analysis to detect SNCG expression in the clinic samples of breast cancer and its correlation with clinical parameters such as tumor size, stage, status of ER, PR, PCNA, and C-erBb2.

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion References

 
Patients and Tissue Specimens.
Breast tissue specimens were obtained from 79 Chinese women accepting operation in Department of Surgery, XinHua Hospital affiliated with Shanghai Second Medical University from September 1999 to July 2002. These patients were randomly selected, including 67 primary breast cancers, 7 breast hyperplasias, and 5 fibroadenomas. The mean age of 67 breast cancer patients was 58.2 years old; among them, 47 cases were older than 50 and 45 cases from the women with menopause. There were 64 cases with tumor size 2 cm and only 3 cases with tumor size < 2 cm. According to the WHO histological classification, 67 breast cancers were composed of 55 infiltrating ductal carcinomas, 4 medullary carcinomas, 3 mucous carcinomas, 2 infiltrating lobular carcinomas, 2 DCISs, and 1 papillary carcinoma. The tumors were staged based on Union International Contre Cancer Tumor-Node-Metastasis classification, including 2 DCISs, 41 stage I/II, and 24 stage III/IV. The issues samples were quickly frozen after surgical removal and stored in liquid nitrogen.

RNA Isolation.
Tissue samples were homogenized in 1 ml of Trizol Reagent (Life Technologies, Inc.; 1 ml/35–45 mg of tissue). The homogenized samples were incubated for 5 min at room temperature. After addition of 0.2 ml of chloroform, the samples were vigorously shaken for 15 s and incubated at room temperature for another 3 min. The samples were then centrifuged at 13,500 rpm for 15 min at 4°C. After the centrifugation, the aqueous phase containing total RNA was transferred to a fresh tube, and the same volume of isopropyl alcohol was added to the tube. The samples were incubated for 10 min at room temperature, and the RNA was precipitated by centrifugation. The RNA pellets were washed with 1 ml of 75% ethanol and dissolved in 40 µl of RNase-free water.

RT-PCR Analyses.
RT-PCR analysis was performed by using a standard RT-PCR with the primers specific for human SNCG and ß-actin. Three µg of total RNAs were used for reverse transcription reaction using oligo(dT)₁₅ primers. The samples were heated to 70°C for 10 min and then quickly chilled on ice. Then, 4 µl of 5x first strand buffer, 2 µl of 0.1 M DTT, 1 µl of 10 mM deoxynucleoside triphosphate, and 200 units of reverse transcriptase were added to the samples. The mixtures were incubated at 42°C for 60 min, and one-fifth of this reaction was amplified by PCR using PCR kit. Each reaction consisted of 30 cycles in the GeneAmp PCR System 2400 (Perkin-Elmer). The parameters for PCR were: denaturation at 95°C for 30 s; annealing at 55°C for 30 s; and elongation at 72°C for 60 s. One-third of the PCR products were electrophoresed through 1% agarose gel. After primers were synthesized and used for amplifying the corresponding genes: (a) human SNCG: 5'-ATGGATGTCTTCAAGAAGGG-3' and 5'-CTAGTCTCCCCCACTCTGGG-3'; and (b) human ß-actin: 5'-GCTGTGCTATCCCTGTACGC-3' and 5'-TGCCTCAGGGCAGCGGAACC-3'.

Immunohistochemical Staining.
As we previously described (21) , deparaffinized, rehydrated, and acid-treated human breast sections (5-µm thick) were treated with H₂O₂, trypsin, and blocked with normal goat serum. Sections were incubated with specific mouse monoclonal antibodies against with ER, PR, C-erBb2, and PCNA (Antibody Diagnostica, Inc.) at 25°C for 30 min followed by the incubation with the biotin-conjugated secondary antirabbit antibodies (Dako). The colorimetric detection was performed by using a standard indirect streptavidin-biotin immunoreaction method by Dako’s Universal LSAB kit according to the manufacturer’s instructions. There were some variations in staining intensity for ER, PR, PCNA, and C-erbB2 expression among the specimens. The positive case was regarded as >20% of tumor cells with immunostaining. Eight fields were randomly selected in each slide were counted under a Nikon microscope at x200 amplification. The negative cases were confirmed with two independent experiments. All stainings were reviewed by two pathologists.

Statistical Analysis.
The data were tested by ² in SPSS10.0. P < 0.05 was consider to be significant.

	Results

Top Abstract Introduction Materials and Methods Results Discussion References

 
Expression of SNCG in Breast Tissue.
Previously, our in situ hybridization analysis has demonstrated an association between SNCG expression and breast cancer progression (1) . To further evaluate the clinical relevance of SNCG expression to breast cancer progression in a large set of clinical specimens, we performed a semiquantitative RT-PCR analysis on 79 clinical breast specimens, including 12 normal or benign lesions, 2 DCISs, 41 stage I/II breast cancers, and 24 stage III/IV breast cancers. As shown in Fig. 1 and summarized in Table 1 , although no SNCG mRNA was detectable in 12 benign breast specimens, SNCG was expressed in most of advanced infiltrating breast cancers. The expression of SNCG mRNA was detectable in 26 of 67 breast cancer cases (38.8%). Among the 26 of SNCG-positive cases, 19 cases were detected in the cancer with stage III/IV, only 6 cases were detected in the cancer with stage I/II, 1 case was detected in DCIS. There was no detectable SNCG mRNA in 3 cases with tumor size < 2 cm. Therefore, SNCG expression is stage specific for breast cancer with no detectable expression in benign lesion, 15% (6 of 41) expression in stage I/II breast carcinomas, and 79% (19 of 24) expression in stage III/IV breast carcinomas.

View larger version (28K): [in this window] [in a new window]   Fig. 1. Expression of SNCG in human breast tissue. Total RNA was isolated from frozen human breast specimens. RT-PCR analysis of SNCG expression was conducted using primers within SNCG-cording sequence as described in "Materials and Methods." The 384-bp PCR product is a specific indication of the presence of SNCG. The integrity and the loading control of the RNA samples were ascertained by actin expression with a set of primers for 314-bp ß-actin. A representative RT-PCR analysis was shown here with 3 benign breast lesions, 3 stage I/II breast cancer cases, and 3 stage III/IV breast cancer cases. The SNCG cDNA plasmid was used as a positive control.

View larger version (143K): [in this window] [in a new window]   Fig. 2. Immunohistochemical analysis of ER, PR, and PCNA. Sections in A–F were stained immunohistochemically with specific antibodies against ER (A and B), PR (C and D), and PCNA (E and F), with brown, indicating ER, PR, and PCNA protein expression in mammary tumor cells. All sections were also counterstained lightly with hematoxylin for viewing nonstained negative cells. The tissue samples were classified into either positive or negative staining. The ER, PR, and PCNA positive sections were defined as >20% of the cells showing positive staining under a light microscope at 200-fold magnification. A, strong nuclear ER staining in almost all infiltrated breast cancer cells. Arrows indicate the positive ER cells. B, negative staining for ER. C, strong nuclear PR staining in >60% of cancer cells. Arrows indicate PR-positive cells. D, negative staining for PR (<10% of cancer cells were PR positive). An arrow indicates the PR-positive cells. E, strong PCNA staining in the highly proliferative cancer cells. F, negative staining for PCNA. For every sample, a serial slide from the same block was also incubated with nonimmunized control IgG, and no significant detectable background staining was observed at the same conditions for each specific antibodies (data not shown).

View larger version (113K): [in this window] [in a new window]   Fig. 3. Immunohistochemical analysis of C-erbB2. Sections were stained immunohistochemically with specific antibodies against C-erbB2 with brown indicating C-erbB2 protein expression in tumor cell membrane. All sections were also counterstained lightly with hematoxylin for viewing nonstained negative cells. A, higher magnification showing (x20) positive C-erbB2 membrane staining (arrows). B, higher magnification showing (x20) negative C-erbB2 membrane staining (open arrows). C, lower magnification showing (x10) positive C-erbB2 membrane staining (arrows). D, lower magnification showing (x10) negative C-erbB2 membrane staining (open arrows). Sections with C-erbB2-positive staining were defined as >20% of counted cells showing positive staining.

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

Previously, Western analysis of SNCG protein expression in human breast tissues showed a similar pattern in that it was not detected in normal breast tissues and stage I/II ductal breast carcinomas but was detected in 70% of stage III/IV ductal breast carcinomas (18) . Ninkina et al. (5) were also able to confirm by using Northern and Western blotting that some breast tumors and breast tumor cell lines expressed SNCG, whereas normal breast tissue did not. Therefore, the stage-specific SNCG expression in breast tissue has been demonstrated, thus far, in three different assays: in situ hybridization analysis (1) ; Western analysis (18) ; and RT-PCR analysis of 79 clinical specimens shown here.

Many predictive and prognostic factors have been proposed and studied for breast cancer. Among them, the most widely used in clinical assessment for breast cancer are ER, PR, PCNA, and C-erbB2. Although expression of SNCG was highly associated with the stage of breast cancer, the status of ER, PR, PCNA, and C-erbB2 were not associated with the stage of breast cancer. It will be interesting to investigate whether SNCG expression in stage I/II cancers may indicate a high risk of malignant progression to more advanced state III/IV tumors. There is cause for concern about the high proportion of breast cancer cases treated with unnecessary mastectomy (22) . If SNCG expression can provide some prognostic information on distinguishing the benign lesions or tumors in early stage that are not likely to become invasive from those that are most likely to become invasive, this will help to direct the treatment strategies and to reduce some inappropriate or unnecessary treatments.

In addition to the link between SNCG and breast cancer progression, it has also been found that synucleins, especially SNCG and SNCB, are involved in ovarian cancer. After our identification of SNCG, Lavedan et al. (4) first suggested that SNCG may be abnormally expressed in ovarian tumors as well as in breast tumors based on the discovery of some SNCG expressed sequence tags in the libraries derived from an ovarian tumor. This suggestion was additionally confirmed by Western and immunohistochemical analyses (18) . Although synuclein (, ß, and ) expression was not detectable by immunohistochemistry in normal ovarian epithelium, 87% (39 of 45) of ovarian carcinomas were found to express at least one type of synuclein, and 42% (19 of 45) expressed all three synucleins (, ß, and ) simultaneously. Highly punctate SNCG expression was also observed in 20% of preneoplastic lesions of the ovary, including epithelial inclusion cysts, hyperplastic epithelium, and papillary structures, suggesting that SNCG up-regulation may occur early in the development of some ovarian tumors (18) .

To elucidate the molecular mechanisms that convert SNCG from a silent gene in normal breast tissue to an actively transcribed gene in breast tumor and to identify upstream regulators of SNCG transcription in neoplastic mammary epithelial cells, we recently isolated a 2195-bp fragment of a human SNCG gene (19) . This fragment includes 1 kb of 5'-flanking region, exon 1, and intron 1. By analyzing the promoter activity and the methylation status, we showed that exon 1 region of SNCG gene contains a CpG island that is unmethylated in SNCG-positive SKBR-3 and T47D cells but densely methylated in SNCG-negative MCF-7 cells. Treating MCF-7 cells with a demethylating agent 5-Aza-2'-deoxycytidine specifically activated SNCG transcription. Thus, our results suggest that aberrant expression of SNCG in breast carcinomas occurs at transcriptional activation by demethylation of exon 1.

The high-level expression of SNCG in the malignant-infiltrating breast epithelial cells suggests that SNCG may play a positive role in breast cancer progression. What role SNCG has in breast and ovary and how it is implicated in breast and ovary cancer remains a mystery. On the basis of our data and others, SNCG has two major functions on the development and progression of mammary tumor: (a) stimulation of cell motility and metastasis; and (b) protection of tumor cells from apoptosis. We have demonstrated that overexpression of SNCG in MDA-MB 435 breast cancer cells led to a significant increase in motility and invasiveness in cell culture and a profound augmentation of metastasis in nude mice (16) . The effect of SNCG on apoptosis in response to several chemotherapy drugs was investigated in ovarian cancer cells (20) . SNCG-expressing cells are significantly more resistant to the chemotherapeutic drugs as compared with the parental cells. Consistent with its antiapoptotic effect, overexpression of SNCG leads to constitutive activation of extracellular signal-regulated protein kinases 1 and 2 and down-regulation of c-Jun NH₂-terminal kinase 1 in response to a host of environmental stress signals, including UV, arsenate, and heat shock. Taken together, these data indicate that oncogenic aberrant SNCG expression contributes to the development of breast and ovarian cancer by promoting tumor cell motility and invasion and tumor cell survival.

	Footnotes

 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported, in part, by American Cancer Society Grant 99-028-04-CCE and United States Army Medical Research and Development Command Grant DAMD17-01-1-0352.

² To whom requests for reprints should be addressed, at Department of Radiation Oncology, Long Island Jewish Medical Center, New Hyde Park, NY 11040. Phone: (718) 470-3086; Fax: (718) 470-9756; E-mail: shi{at}lij.edu

³ The abbreviations used are: BCSG1, breast cancer specific gene 1; AD, Alzheimer’s disease; ER, estrogen receptor; PD, Parkinson’s disease; PR, progesterone receptor; SNCA, synuclein; SNCB, ß synuclein; SNCG, synuclein; RT-PCR, reverse transcription-PCR; PCNA, proliferating cell nuclear antigen; DCIS, ductal carcinoma in situ.

Received 2/28/03; revised 6/10/03; accepted 6/12/03.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Ji H., Liu Y. E., Jia T., Wang M., Liu J., Joseph B. K., Rosen C., Shi Y. E. Identification of a breast cancer-specific gene, SNCG, by direct differential complementary DNA sequencing. Cancer Res., 57: 759-764, 1997.[Abstract/Free Full Text]
2. Shi Y. E., Ni J., Xiao G., Liu Y. E., Fuchs A., Yu G., Cosgrove J. M., Xing L., Zhang M., Li J., Aggarwal B. B., Meager A., Gentz R. Antitumor activity of the novel human breast cancer growth inhibitor MRG. Cancer Res., 57: 3084-3091, 1997.[Abstract/Free Full Text]
3. Xiao G., Liu Y. E., Gentz R., Sang Q. A., Ni J., Goldberg I. D., Shi Y. E. Suppression of breast cancer growth and metastasis by a serpin myoepithelium-derived serine proteinase inhibitor expressed in the mammary myoepithelial cells. Proc. Natl. Acad. Sci. USA, 96: 3700-3705, 1999.[Abstract/Free Full Text]
4. Lavedan C., Leroy E., Dehejia A., Buchholtz S., Dutra A., Nussbaum R. L., Polymeropoulos M. H. Identification, localization and characterization of the human -synuclein gene. Hum. Genet., 103: 106-112, 1998.[Medline]
5. Ninkina N., Alimova-Kost M., Paterson J., Delaney L., Cohen B., Imreh S., Gnuchev N., Davies A., Buchman V. Organisation, expression and polymorphism of the human persyn gene. Hum. Mol. Genet., 7: 1417-1424, 1998.[Abstract/Free Full Text]
6. Clayton D. F., George J. M. The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci., 21: 249-254, 1998.[Medline]
7. Lavedan C. The synuclein family. Genome Res., 8: 871-880, 1998.[Abstract/Free Full Text]
8. George J. M. The synucleins. Genome Biol., 3: 3002.1-3002.6, 2001.
9. Polymeropoulos M. H., Lavedan C., Leroy E., Ide S. E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R., Stenroos E. S., Chandrasekharappa S., Athanassiadou A., Papapetropoulos T., Johnson W. G., Lazzarini A. M., Duvoisin R. C., Di Iorio G., Golbe L. I., Nussbaum R. L. Mutation in the -synuclein gene identified in families with Parkinson’s disease. Science (Wash. DC), 276: 2045-2047, 1997.[Abstract/Free Full Text]
10. Spillantini M. G., Schmidt M. L., Lee V. M., Trojanowski J. Q., Jakes R., Goedert M. -Synuclein in Lewy bodies. Nature (Lond.), 388: 839-840, 1997.[Medline]
11. Takeda A., Mallory M., Sundsmo M., Honer W., Hansen L., Masliah E. Abnormal accumulation of NACP/-synuclein in neurodegenerative disorders. Am. J. Pathol., 152: 367-372, 1998.[Abstract]
12. Ueda K., Fukushima H., Masliah E., Xia Y., Yoshimoto M., Otero D. A., Kondo J., Ihara Y., Saitoh T. Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc. Natl. Acad. Sci. USA, 90: 11282-11286, 1993.[Abstract/Free Full Text]
13. Yoshimoto M., Iwai A., Kang D., Otero D. A., Xia Y., Saitoh T. NACP, the precursor protein of the non-amyloid ß/A4 protein (A ß) component of Alzheimer disease amyloid, binds A ß and stimulates A ß aggregation. Proc. Natl. Acad. Sci. USA, 92: 9141-9145, 1995.[Abstract/Free Full Text]
14. Duda J. E., Lee V. M., Trojanowski J. Q. Neuropathology of synuclein aggregates. J. Neurosci. Res., 61: 121-127, 2000.[Medline]
15. Galvin J. E., Uryu K., Lee V. M., Trojanowski J. Q. Axon pathology in Parkinson’s disease and Lewy body dementia hippocampus contains -, ß-, and -synuclein. Proc. Natl. Acad. Sci. USA, 96: 13450-13455, 1999.[Abstract/Free Full Text]
16. Jia T., Liu Y. E., Liu J., Shi Y. E. Stimulation of breast cancer invasion and metastasis by synuclein . Cancer Res., 59: 742-747, 1999.[Abstract/Free Full Text]
17. Liu J., Spence M. J., Zhang Y. L., Jiang Y., Liu Y. E., Shi Y. E. Transcriptional suppression of synuclein (SNCG) expression in human breast cancer cells by the growth inhibitory cytokine oncostatin M. Breast Cancer Res. Treat., 62: 99-107, 2000.[Medline]
18. Bruening W., Giasson B. I., Klein-Szanto A. J., Lee V. M., Trojanowski J. Q., Godwin A. K. Synucleins are expressed in the majority of breast and ovarian carcinomas and in preneoplastic lesions of the ovary. Cancer (Phila.), 88: 2154-2163, 2000.
19. Lu A., Gupta A., Li C., Ahlborn T. E., Ma Y., Shi Y. E., Liu J. Molecular mechanisms for aberrant expression of the human breast cancer specific gene 1 in breast cancer cells: control of transcription by DNA methylation and intronic sequences. Oncogene, 20: 5173-5185, 2001.[Medline]
20. Pan Z. Z., Bruening W., Giasson B. I., Lee V. M., Godwin A. K. -Synuclein promotes cancer cell survival and inhibits stress- and chemotherapeutic drug-induced apoptosis by modulating MAPK pathways. J. Biol. Chem., 277: 35050-35060, 2002.[Abstract/Free Full Text]
21. Wang M., Liu Y. E., Ni J., Aygun B., Goldberg I. D., Shi Y. E. Induction of mammary differentiation by mammary-derived growth inhibitor-related gene that interacts with an -3 fatty acid on growth inhibition of breast cancer cells. Cancer Res., 60: 6482-6487, 2000.[Abstract/Free Full Text]
22. Ernster V. L., Barclay J., Kerlikowske K., Grady D., Henderson C. Incidence of and treatment for ductal carcinoma in situ of the breast. J. Am. Med. Assoc., 275: 913-918, 1996.[Abstract]

This article has been cited by other articles:

				M. Ahmad, S. Attoub, M. N. Singh, F. L. Martin, and O. M. A. El-Agnaf {gamma}-Synuclein and the progression of cancer FASEB J, November 1, 2007; 21(13): 3419 - 3430. [Abstract] [Full Text] [PDF]

				V. K. Singh, Y. Zhou, J. A. Marsh, V. N. Uversky, J. D. Forman-Kay, J. Liu, and Z. Jia Synuclein-{gamma} Targeting Peptide Inhibitor that Enhances Sensitivity of Breast Cancer Cells to Antimicrotubule Drugs Cancer Res., January 15, 2007; 67(2): 626 - 633. [Abstract] [Full Text] [PDF]

				H. Liu, W. Liu, Y. Wu, Y. Zhou, R. Xue, C. Luo, L. Wang, W. Zhao, J.-D. Jiang, and J. Liu Loss of Epigenetic Control of Synuclein-{gamma} Gene as a Molecular Indicator of Metastasis in a Wide Range of Human Cancers Cancer Res., September 1, 2005; 65(17): 7635 - 7643. [Abstract] [Full Text] [PDF]

				M. J. Naylor, S. R. Oakes, M. Gardiner-Garden, J. Harris, K. Blazek, T. W. C. Ho, F. C. Li, D. Wynick, A. M. Walker, and C. J. Ormandy Transcriptional Changes Underlying the Secretory Activation Phase of Mammary Gland Development Mol. Endocrinol., July 1, 2005; 19(7): 1868 - 1883. [Abstract] [Full Text] [PDF]

				D. Cui, G. Jin, T. Gao, T. Sun, F. Tian, G. G. Estrada, H. Gao, and A. Sarai Characterization of BRCAA1 and Its Novel Antigen Epitope Identification Cancer Epidemiol. Biomarkers Prev., July 1, 2004; 13(7): 1136 - 1145. [Abstract] [Full Text] [PDF]

				Y. Jiang, Y. E. Liu, I. D. Goldberg, and Y. E. Shi {gamma} Synuclein, a Novel Heat-Shock Protein-Associated Chaperone, Stimulates Ligand-Dependent Estrogen Receptor {alpha} Signaling and Mammary Tumorigenesis Cancer Res., July 1, 2004; 64(13): 4539 - 4546. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, K. Articles by Shi, Y. E. Search for Related Content PubMed PubMed Citation Articles by Wu, K. Articles by Shi, Y. E.