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TGF-ß signaling (brown) keeps stem cells dormant but alive in the proximal prostate.

Prostate cancer and benign prostatic hyperplasia result from excessive proliferation of cells in this organ, likely due to deregulation of stem cells. Salm et al. (page 81) find that cells in the proximal region of the prostate, where the stem cells reside, respond differently to TGF-ß relative to distal cells in mice. A regulatory teeter-totter between TGF-ß expression, which inhibits cell proliferation and pro-growth cytokines, maintains stem cell quiescence in the healthy organ.

The researchers looked first at androgen-expressing animals. They found that cells in the proximal region of the prostate had more TGF-ß–mediated signaling than did cells in the distal region. This should keep the stem cells quiescent, but the cells still survive, probably because of the high expression of anti-apoptotic Bcl-2 in the region.

The distal region normally has lower TGF-ß signaling, but androgen withdrawal reversed the pattern. Now the high TGF-ß in the distal region induced apoptosis, whereas the lowered TGF-ß signaling in the proximal region allowed stem cells in this area to respond to pro-growth cytokines.

The balance between TGF-ß and pro-growth cytokines likely maintains the quiescent state of stem cells in a healthy prostate, and deregulation may lead to prostate disease. A similar balancing act may also be present in the epidermal and hematopoietic stem cells already known to be regulated by TGF-ß.

Rabiya S. Tuma

rabiya{at}nasw.org

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TGF-ß maintains dormancy of prostatic stem cells in the proximal region of ducts

Sarah N. Salm, Patricia E. Burger, Sandra Coetzee, Ken Goto, David Moscatelli, and E. Lynette Wilson
J. Cell Biol. 2005 170: 81-90. [Abstract] [Full Text] [PDF]

PPT slides of all figures This Article Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tuma, R. S. Search for Related Content PubMed Articles by Tuma, R. S. Related Collections Related Article Social Bookmarking                      What's this?