A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Academic Article uri icon

Overview

abstract

  • Prostate cancer progresses from a hormone-sensitive, androgen-dependent stage to a hormone-refractory, androgen-independent tumor. The androgen receptor pathway functions in these androgen-independent tumors despite anti-androgen therapy. In our LAPC-4 prostate cancer model, androgen-independent sublines expressed higher levels of the HER-2/neu receptor tyrosine kinase than their androgen-dependent counterparts. Forced overexpression of HER-2/neu in androgen-dependent prostate cancer cells allowed ligand-independent growth. HER-2/neu activated the androgen receptor pathway in the absence of ligand and synergized with low levels of androgen to 'superactivate' the pathway. By modulating the response to low doses of androgen, a tyrosine kinase receptor can restore androgen receptor function to prostate cancer cells, a finding directly related to the clinical progression of prostate cancer.

publication date

  • March 1, 1999

Research

keywords

  • Androgens
  • Prostatic Neoplasms
  • Receptor, ErbB-2
  • Receptors, Androgen
  • Signal Transduction

Identity

Scopus Document Identifier

  • 0033022342

Digital Object Identifier (DOI)

  • 10.1038/6495

PubMed ID

  • 10086382

Additional Document Info

volume

  • 5

issue

  • 3