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Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses
Published on: October 24, 2019
Loss of PTEN is associated with progression to androgen independence
Jerod Bertram1, James W Peacock, Ladan Fazli
1The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Background:
Progression to a lethal androgen-independent (AI) stage of advanced prostate cancer is a critical clinical obstacle limiting patient survival. PTEN inactivation is frequently observed in advanced prostate cancer and correlates with a poor prognosis. However, the functional significance of PTEN inactivation in AI progression has not been demonstrated.
Methods:
PTEN expression was examined in benign, hormone naïve and AI human prostate cancer specimens, and in recurrent AI Shionogi tumors. The effect of antisense oligonucleotide (ASO)-mediated PTEN downregulation in AI progression of the Shionogi tumor model was determined.
Results:
Significantly reduced PTEN expression was observed in AI versus benign and hormone naïve prostate tumors. Seven of 14 AI Shionogi tumors exhibited marked downregulation or complete loss of PTEN. ASO-mediated PTEN inhibition reduced androgen-withdrawal induced regression of Shionogi tumors and accelerated AI progression.
Conclusions:
These data suggest that PTEN inactivation may play a role in progression to androgen independence.
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