Regulating the prostate
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《细胞学杂志》
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-? relative to distal cells in mice. A regulatory teeter-totter between TGF-? 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-?–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-? signaling, but androgen withdrawal reversed the pattern. Now the high TGF-? in the distal region induced apoptosis, whereas the lowered TGF-? signaling in the proximal region allowed stem cells in this area to respond to pro-growth cytokines.
The balance between TGF-? 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-?.(TGF-? signaling (brown) keeps stem cells)
The researchers looked first at androgen-expressing animals. They found that cells in the proximal region of the prostate had more TGF-?–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-? signaling, but androgen withdrawal reversed the pattern. Now the high TGF-? in the distal region induced apoptosis, whereas the lowered TGF-? signaling in the proximal region allowed stem cells in this area to respond to pro-growth cytokines.
The balance between TGF-? 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-?.(TGF-? signaling (brown) keeps stem cells)