Identification and characterization of estrogen receptor variants in prostate cancer cell lines

Ye, QN Chung, LWK Cinar, B Li, SW Zhau, HE

Qn. Ye et al., Identification and characterization of estrogen receptor variants in prostate cancer cell lines, J STEROID B, 75(1), 2000, pp. 21-31

37

INGLESE

Article

Biochemistry & Biophysics

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

0960-0760 → ACNP

75

1

2000

21 - 31

ISI

0960-0760(200012)75:1<21:IACOER>2.0.ZU;2-Z

A sensitive semi-nested reverse transcriptase-polymerase chain reaction (RT -PCR) amplification was performed to evaluate estrogen receptor-alpha (ER-a lpha) mRNA expression in prostate cancer cell lines. We demonstrated the pr esence of wild-type ER-alpha (wt ER-cl) and five ER-rx variants, designated ER-alphaA, B, C, D, and E, Unlike ER-alphaA and D, ER-alpha B, C, and E we re not previously reported in normal or cancerous mammalian cells. DNA sequ encing analysis of these ER-alpha variants revealed the genetic changes to be either in-frame or out-of-frame deletions. The expression of each ER-alp ha variant differs significantly depending on the androgen responsiveness, tumorigenic and metastatic potentials of each prostate cancer cell line. Th e potential functional significance of ER-alpha variants was assessed in ye ast two-hybrid and ERE promoter-reporter mammalian transcription assay syst ems. The results of these studies indicated that none of the ER-alpha varia nts can form homo- or heterodimers either with wt ER-alpha or among themsel ves: in vivo, and that these ER-alpha variants have no demonstrable transcr iptional or dominant-negative activity, as assessed in vitro. (C) 2001 Else vier Science Ltd. All rights reserved.