Mechanism of and Requirement for Estrogen-regulated MYB Expression in Estrogen-receptor-positive Breast Cancer Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Aug 11

PMID 17690249

Citations 73

Authors

Yvette Drabsch

Honor Hugo

Rui Zhang

Dennis H Dowhan

Yu Rebecca Miao

Alan M Gewirtz

Simon C Barry

Robert G Ramsay

Thomas J Gonda

Affiliations

Soon will be listed here.

Abstract

MYB (the human ortholog of c-myb) is expressed in a high proportion of human breast tumors, and that expression correlates strongly with estrogen receptor (ER) positivity. This may reflect the fact that MYB is a target of estrogen/ER signaling. Because in many cases MYB expression appears to be regulated by transcriptional attenuation or pausing in the first intron, we first investigated whether this mechanism was involved in estrogen/ER modulation of MYB. We found that this was the case and that estrogen acted directly to relieve attenuation due to sequences within the first intron, specifically, a region potentially capable of forming a stem-loop structure in the transcript and an adjacent poly(dT) tract. Secondly, given the involvement of MYB in hematopoietic and colon tumors, we also asked whether MYB was required for the proliferation of breast cancer cells. We found that proliferation of ER(+) but not ER(-) breast cancer cell lines was inhibited when MYB expression was suppressed by using either antisense oligonucleotides or RNA interference. Our results show that MYB is an effector of estrogen/ER signaling and provide demonstration of a functional role of MYB in breast cancer.

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