Michael Ittmann Lab

Cellular senescence and prostate cancer


Prostate cancer is a disease characterized by a markedly increased incidence with age. Research in our laboratory has established that fibroblast growth factors act as important growth and survival factors for prostate cancer cells. Our fundamental hypothesis is that increased expression of FGFs by normal tissue in the peripheral zone of the prostate acts as stimulus to prostate cancer progression by providing critical growth and survival signals to adjacent prostate cancer cells. A corollary of this hypothesis is that individual variation in the control of expression of these progression factors may lead to differences in the incidence of prostate cancer.

Recent work in our laboratory has shown cellular senescence of prostatic epithelial cells leads to expression of cytokines which in turn induce expression of FGFs by stromal cells that then act as growth factors for prostate cancer cells and in this manner promote prostate cancer progression. If so, variation in the extent of cellular senescence may explain differences in disease incidence. Our current data strongly supports this hypothesis and indicates that oxidative DNA damage is a major determinant of cellular senescence in prostatic epithelium.