Biochemistry Graduate Seminar
Monday, October 19, 2009
Lecture at 4:30 p.m. in Burt Hall 114
Coffee at 4:15 p.m. in Chalmers 168
Debarshi Banerjee
A novel role of gap junction connexin46 protein
to protect cells from hypoxia-induced death
Connexin proteins are the principle structural components of the gap junctions. Colocalization and tissue-specific expression of diverse connexin molecules are reported to occur in a variety of organs. Impairment of gap junctional intercellular communication, caused by mutations, gain of function, or loss of function of connexins, is involved in a number of diseases including the development of cancer. Here we show that human breast cancer cells, MCF-7, and breast tumor tissues express a novel gap junction protein, connexin 46 (Cx46) and it plays a critical role in hypoxia. Previous studies have shown that connexin46 is predominantly expressed in lens and our studies find that Cx46 protects human lens epithelial cells (HLEC) from hypoxia induced death. Interestingly, we find that Cx46 is upregulated in MCF-7 breast cancer cells and human breast cancer tumors. Downregulation of Cx46 by siRNA promotes 40% MCF-7 cell death at 24 hour under hypoxic conditions. Furthermore, direct injection of anti-Cx46 siRNA into xenograft tumors prevents tumor growth in nude mice. Our data suggests that both normal hypoxic tissue (lens) and adaptive hypoxic tissue (breast tumor) may utilize the same protein, Cx46, as a protective strategy from hypoxia.