Connexins in Prostate Cancer Initiation and Progression
Revised final rept. 1 Sep 2009-31 Aug 2013
NEBRASKA UNIV AT OMAHA
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The role of cell-cell contact-dependent communication in the progression of prostate cancer from a slowgrowing hormone androgen-dependent state to a highly malignant, hormone-independent state is not fully understood. Gap junctions, formed of proteins called connexins, provide a direct intercellular communication pathway for the passage of small growth regulatory signaling molecules between the cytoplasmic interiors of adjoining cells. Mutations in various connexin genes have been detected in a wide variety of diseases related to differentiation and proliferation. Connexins have been now documented to be legitimate tumor suppressors. Our studies have shown that epithelial cells from prostate tumors show subtle alterations in the expression of connexins in vivo and in vitro. These alterations include intracellular accumulation of connexins in aggressive prostate tumors and their impaired trafficking and assembly into gap junctions. Re-expression of connexins in connexin-deficient, indolent prostate cancer cell line, LNCaP, retards growth in vivo and in vitro and induces differentiation.
- Medicine and Medical Research