Androgen receptor (AR) expression in AR-negative prostate cancer cells results in differential effects of DHT and IGF-I on proliferation and AR activity between localized and metastatic tumors

The Prostate
Stephen R PlymateJ L Ware

Abstract

Two features of the progression from organ-confined to metastatic prostate cancer are dysregulation of the androgen receptor (AR) and a decrease in insulin-like growth factor-type-I receptor (IGF-IR) expression. The purpose of this study was to determine the effect of changes in IGF-IR expression on AR activity. M12 human prostate cells were stably transfected with an AR expression construct to produce the M12-AR parental (PAR) cell line. PAR cells were implanted orthotopically into nude mice and M12-AR primary (PRI) cell lines were derived from intraprostatic tumors and metastatic cell lines (MET) were derived from PRI tumors that had metastasized to diaphragm or lung. Tumor formation in the prostate by PAR cells was decreased significantly compared to M12 controls. PAR, PRI, and MET cells expressed equivalent amounts of AR protein; however, IGF-IR expression was increased significantly in PAR and PRI cells. IGF-IR expression decreased in MET lines to the levels seen in M12 control cells. IGF-I significantly enhanced dihydrotestosterone (DHT)-stimulated, but not basal, AR transcriptional activity in PRI cells. In MET cells, IGF-I significantly suppressed DHT-stimulated transcriptional activity. In MET cells in which the IGF-IR...Continue Reading

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Citations

Nov 26, 2008·Journal of Mammary Gland Biology and Neoplasia·Deepali Sachdev
Jul 21, 2010·The Journal of Clinical Investigation·Shihua SunStephen R Plymate
Jan 1, 2007·Indian Journal of Urology : IJU : Journal of the Urological Society of India·J S GirlingD E Neal
Apr 28, 2006·Journal of Cellular Biochemistry·Jennifer D WuStephen R Plymate
Aug 5, 2005·Genes, Chromosomes & Cancer·Shahriar KoochekpourOliver Sartor
Apr 6, 2011·Journal of Cellular Physiology·Aejaz SayeedLucia R Languino
Oct 10, 2013·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Fábio MonticoValéria Helena Alves Cagnon
Sep 2, 2006·Critical Reviews in Oncology/hematology·H G van der Poel
Nov 15, 2015·Journal of Hematology & Oncology·Michael T Schweizer, Evan Y Yu
Mar 9, 2005·Cancer Research·Giuseppe PandiniAntonino Belfiore

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