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The estrogen and c-Myc target gene HSPC111 is over-expressed in breast cancer and associated with poor patient outcome.

Abstract：

INTRODUCTION:Estrogens play a pivotal role in the initiation and progression of breast cancer. The genes that mediate these processes are not fully defined, but potentially include the known mammary oncogene MYC. Characterization of estrogen-target genes may help to elucidate further the mechanisms of estrogen-induced mitogenesis and endocrine resistance. METHODS:We used a transcript profiling approach to identify targets of estrogen and c-Myc in breast cancer cells. One previously uncharacterized gene, namely HBV pre-S2 trans-regulated protein 3 (HSPC111), was acutely upregulated after estrogen treatment or inducible expression of c-Myc, and was selected for further functional analysis using over-expression and knock-down strategies. HSPC111 expression was also analyzed in relation to MYC expression and outcome in primary breast carcinomas and published gene expression datasets. RESULTS:Pretreatment of cells with c-Myc small interfering RNA abrogated estrogen induction of HSPC111, identifying HSPC111 as a potential c-Myc target gene. This was confirmed by the demonstration of two functional E-box motifs upstream of the transcription start site. HSPC111 mRNA and protein were over-expressed in breast cancer cell lines and primary breast carcinomas, and this was positively correlated with MYC mRNA levels. HSPC111 is present in a large, RNA-dependent nucleolar complex, suggesting a possible role in ribosomal biosynthesis. Neither over-expression or small interfering RNA knock-down of HSPC111 affected cell proliferation rates or sensitivity to estrogen/antiestrogen treatment. However, high expression of HSPC111 mRNA was associated with adverse patient outcome in published gene expression datasets. CONCLUSION:These data identify HSPC111 as an estrogen and c-Myc target gene that is over-expressed in breast cancer and is associated with an adverse patient outcome.

journal_name

Breast Cancer Res

journal_title

Breast cancer research : BCR

authors

Butt AJ,Sergio CM,Inman CK,Anderson LR,McNeil CM,Russell AJ,Nousch M,Preiss T,Biankin AV,Sutherland RL,Musgrove EA

doi

10.1186/bcr1985

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

R28

issue

eissn

1465-5411

issn

1465-542X

pii

bcr1985

journal_volume

pub_type

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The estrogen and c-Myc target gene HSPC111 is over-expressed in breast cancer and associated with poor patient outcome.