Restoring Sensitivity to Apoptosis in Prostate Cancer Cells by Reconstitution of the Tumor Suppressor PTEN

摘要

Metastatic prostate cancer almost invariably ably progresses to the terminal stage despite treatment such as androgen deprivation and chemotherapy and radiation therapy. This resistance to treatment may be due to the resistance to apoptosis in cancer cells. Therefore understanding the molecular basis for resistance to apoptosis is essential for devising novel strategies to sensitize cancer cells to apoptosis We have been focused on the role of the tumor suppressor PTEN in regulating sensitivity to apoptosis in prostate cancer. We have previously shown that loss of HEN function leads to excessive antiapoptotic signaling through constitutive activation of the Akt protein kinase. Therefore, we proposed that restoration of HEN expression may lead to sensitization to apoptotic stimuli such as proapoptotic ligands and chemotherapeutic agents. Over the funding period of this proposal, we have made significant contributions toward substantiating this hypothesis. We have also generated significant data toward the effect of the HEN signaling pathway in two important transcription factors, NF-kB and the androgen receptor. Our work over the funding period has resulted in 4 published or submitted full-length articles and two abstracts presented at national scientific meetings.