Increased S6K1 protein expression confers proliferative advantage and Rapamycin sensitivity to human mammary cancer cells

CHED 972

Nilly Brodt, ylr14@aol.com1, Rachel L. Yamnik, ylr14@aol.com1, John Blenis, John_Blenis@hms.harvard.edu2, and Marina K. Holz, marina_holz@post.harvard.edu1. (1) Department of Biology, Stern College for Women, Yeshiva University, 245 Lexington Avenue, New York, NY 10016, (2) Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115
Mammalian Target of Rapamycin is a protein kinase which contributes to cell growth regulation (reviewed in Fingar and Blenis, 2004). Rapamycin, a naturally-occurring bacterially-derived drug which inhibits mTOR, possesses immunosuppressive activity and potential for tumor growth inhibition. mTOR mediates growth through increased protein synthesis by phosphorylating several proteins, including S6Kinase1. S6K1 targets the 40S ribosomal subunit's S6 protein, thereby representing a vital moderator of mTOR-dependent cell cycle control. (Fingar et al., 2004). We examined growth of mammary cell lines expressing different S6K1 levels and report that S6K1 expression correlates to differences in cell proliferation, depending on growth conditions. While S6K1 overexpression does not confer proliferative advantage in full, or the absence of, serum, it does correlate to increased proliferation in low serum and to growth hindrance in presence of Rapamycin. Our future research includes assessing the proliferation capacity of cancerous mammary cell lines exhibiting S6K1 knock-down in varying growth conditions.