Human Genetics Training Program

Professor of Oncology and Pathology

Room 410, Cancer Research Building
410-614-2479
410-614-4073 (Fax)
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The goal of the laboratory is to identify gene alterations, to study the consequences of these changes to the cellular machinery, and to translate this knowledge to early detection and novel therapies for breast cancer. We have identified a large number of candidate oncogenes and tumor suppressor genes by SAGE and microarray analysis. Among these, we are currently analyzing tight junction proteins, Claudin-3, -4 and 7 and the homeotic genes, HOXA5 and HOXB7. HOXA5 is a potent transcriptional regulator of the progesterone receptor and the p53 gene, and its expression is lost in breast cancer cells. Few HOXA5 minus mice survive; the females have defects in lactation. HOXB7, on the other hand, is over expressed in breast cancer, and induces production of growth factors in cancer cells.

Study of mammary development and breast tumorigenesis in conditional knockout mice for HOXA5, and in transgenic mice overexpressing HOXB7.

Role of Claudin-7 in metastasis using imaging techniques, mammary development in transgenic mice and proteomic analysis of genes induced by Claudin-7 overexpression.

• Chen H, Chung S and Sukumar S. Hoxa5-induced apoptosis in breast cancer cells is mediated by caspases 2 and 8. Molecular Cellular Biology, 24: 924-935, 2004.
• Mehrotra J, Ganpat MM, Kanaan Y, Fackler MJ, McVeigh M, Lahti-Domenici J, Polyak, K, Argani P, Naab, T, Garrett E, Parmigiani G, Broome C and Sukumar S. ER/PR-negative breast cancers of young African American women have a higher frequency of methylation of multiple genes than those of Caucasian women. Clin Cancer Res. 10:2052-2057, 2004.
• Zhu T, and Sukumar S. Coupling the transcriptional regulatory action of brn-3b to the cell cycle clock. Cancer Biol and Therapy, 3: 324-325, 2004.
• Kominsky SL, Vali M, Korz M, Gabig TG, Garrett E, Argani P, and Sukumar S. Clostridium perfringens enterotoxin elicits rapid and specific cytolysis of breast carcinoma cells mediated through tight junction proteins Claudin 3 and 4. Amer J Pathol, 164:1627-1633, 2004.
• Mehrotra J, Vali M, McVeigh M, Kominsky SL, Fackler MJ, Lahti-Domenici J, Polyak K, Sacchi N, Argani P, and Sukumar S. Very high frequency of hypermethylated genes in breast cancer metastasis to the bone, brain, and lung. Clin Cancer Res. 10: 3104-3109, 2004.
• Fackler MJ, McVeigh M, Mehrotra J, Blum MA, Lange J, Lapides A, Garrett E, Argani P, and Sukumar S. Quantitative multiplex methylation specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer. Cancer Res. 64:4442-4452, 2004.
• Parker BS, Argani P, Cook BP, Han L, Chatrand SD, Zhang M, Saha S, Bardelli A, Yiang Y, St. Martin TB, Nacht M, Teicher B, Klinger KW, Sukumar S, and Madden S. Alterations in vascular gene expression in invasive breast carcinoma. Cancer Res.64: 7857-7866 2004.
• Fackler, MJ, McVeigh M, Evron E, Garrett E, Mehrotra J, Polyak, Sukumar S, Argani P. DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma. Int. Journal of Cancer 107, 970-975, 2003.