LEF1 in androgen-lndependent prostate cancer: regulation of androgen receptor expression, prostate cancer growth, and invasion

Yirong Li, Longgui Wang, Miao Zhang, Jonathan Melamed, Xiaomei Liu, Robert Reiter, Jianjun Wei, Yi Peng, Xuanyi Zou, Angel Pellicer, Michael J. Garabedian, Anna Ferrari, Peng Lee

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

A major obstacle in treating prostate cancer is the development of androgen-independent disease. In this study, we examined LEF1 expression in androgen-independent cancer as well as its regulation of androgen receptor (AR) expression, prostate cancer growth, and invasion in androgenindependent prostate cancer cells. Affymetrix microarray analysis of LNCaP and LNCaP-AI (androgen-independent variant LNCaP) cells revealed 100-fold increases in LEF1 expression in LNCaP-AI cells. We showed that LEF1 overexpression in LNCaP cells resulted in increased AR expression and consequently enhanced growth and invasion ability, whereas LEF1 knockdown in LNCaP-AI cells decreased AR expression and, subsequently, growth and invasion capacity. Chromatin immunoprecipitation, gel shift, and luciferase assays confirmed LEF1 occupancy and regulation of the AR promoter. Thus, we identified LEF1 as a potential marker for androgen-independent disease and as a key regulator of AR expression and prostate cancer growth and invasion. LEF1 is highly expressed in androgen-independent prostate cancer, potentially serving as a marker for androgen-independent disease.

Original languageEnglish (US)
Pages (from-to)3332-3338
Number of pages7
JournalCancer Research
Volume69
Issue number8
DOIs
StatePublished - Apr 15 2009

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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