Cooperativity Between Oncogenic PKC Epsilon and Pten Loss in Prostate Cancer Progression
Annual rept. 30 Sep 2014-29 Sep 2015
TRUSTEES OF PENNSYLVANIA UNIV PHILADELPHIA PA
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The main objective of our studies is to elucidate the mechanisms by which PKC-epsilon in conjunction with Pten loss, lead to malignant transformation and metastasis, through an autocrine mechanism that involves the release of the chemokine CXCL13. During the first year we acquired new evidence that CXCL13 levels are elevated in prostate cancer cells and that PKC-epsilon is causally associated with the elevated production and release of this chemokine. We also initiated studies to dissect the signaling mechanisms that mediate CXCL13 induction. We took advantage of a cellular model that we generated in our laboratory in which PKC-epsilon was overexpressed using a lentivirus in a Pten-deficient background. We also remediated the issue of loss of stable PKC-epsilon expression in prostate epithelial cell lines by generating a new PKC-epsilon lentivirus. Our research may impact on our understanding of the molecular mechanisms of prostate tumorigenesis, and may have significant prognostic and therapeutic implications.
- Anatomy and Physiology
- Medicine and Medical Research