page 81) find that cells in the proximal region of the prostate, where the stem cells reside, respond differently to TGF-β relative to distal cells in mice. A regulatory teeter-totter between TGF-β 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-β–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-β signaling, but androgen withdrawal reversed the pattern. Now the high TGF-β in the distal region induced apoptosis, whereas the lowered TGF-β signaling in the proximal region allowed stem cells in this area to respond to pro-growth cytokines.
The balance between TGF-β 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-β.