The Role of Skp2 in the Prostate Tumorigenesis Following Rb and p53 Loss
Technical Report,26 Sep 2013,25 Sep 2015
Albert Einstein College of Medicine Bronx United States
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pRb and p53 are the two of the best known tumor suppressor proteins. They play key roles in provide most and best of the cells intrinsic antitumor mechanisms, such as proliferation arrest, cellular senescence, and apoptosis. pRb and p53 are frequently inactivated in cancer. Reactivating pRb and p53 is a major goal of anticancer strategies. While many investigators have studied and successfully demonstrated the importance of pRb and p53 in tumor suppression by deleting Rb1 or TP53 to establish various mouse tumor models, very few cancer researchers have attempted to inhibit tumorigenesis in models that mutate both pRb and p53. Indeed, it was not known whether pRb and p53 doubly deficient tumorigenesis could be blocked without resorting Relative gene expressionfolds change0.05.010.015.020.0CD49f Sca-1WTSkp2KODKOTKOFigure 7. Quantitative analysis of Q-PCR prostate stem cell marker genes CD49f and Sca-1 in prostates from 3-4 month old mice12to severe measures that are incompatible with normal cell proliferation. This research demonstrated unequivocally that pRb and p53 doubly deficient tumorigenesis can be completely blocked at least in the mouse prostate. Moreover, this research has achieved this by deleting a molecule Skp2 that can be targeted without causing major defects in cell proliferation and mouse development. Thus, in this work, I have identified a vulnerability of pRb and p53 doubly deficient tumor cells, which can potentially be exploited therapeutically. In addition, this study provides a cause for optimism, by showing that we can anticipate finding therapeutic strategies that are effective against highly aggressive cancers, such as those lacking RB1 and TP53.