The expression of the ubiquitin ligase SIAH (seven in absentia homolog) 2 is mediated through gene copy number in breast cancer and is associated with a basal-like phenotype and p53 expression

Chan, Peter, Möller, Andreas, Liu, Mira C. P., Sceneay, Jaclyn E., Wong, Christina S. F., Waddell, Nic, Huang, Katie T., Dobrovic, Alexander, Millar, Ewan K. A., O'Toole, Sandra A., McNeil, Catriona M., Sutherland, Robert L., Bowtell, David D. and Fox, Stephen B. (2011) The expression of the ubiquitin ligase SIAH (seven in absentia homolog) 2 is mediated through gene copy number in breast cancer and is associated with a basal-like phenotype and p53 expression. Breast Cancer Research, 13 1: R19. doi:10.1186/bcr2828


Author Chan, Peter
Möller, Andreas
Liu, Mira C. P.
Sceneay, Jaclyn E.
Wong, Christina S. F.
Waddell, Nic
Huang, Katie T.
Dobrovic, Alexander
Millar, Ewan K. A.
O'Toole, Sandra A.
McNeil, Catriona M.
Sutherland, Robert L.
Bowtell, David D.
Fox, Stephen B.
Title The expression of the ubiquitin ligase SIAH (seven in absentia homolog) 2 is mediated through gene copy number in breast cancer and is associated with a basal-like phenotype and p53 expression
Journal name Breast Cancer Research   Check publisher's open access policy
ISSN 1465-5411
1465-542X
Publication date 2011
Sub-type Article (original research)
DOI 10.1186/bcr2828
Open Access Status DOI
Volume 13
Issue 1
Start page R19
Total pages 10
Place of publication United Kingdom
Publisher Current Medicine Group Ltd.
Collection year 2012
Language eng
Formatted abstract
Introduction:
SIAH2 plays a significant role in the hypoxic response by regulating the abundance of HIF-1alpha, however, its role in breast carcinoma is unclear. We investigated the frequency and expression pattern of SIAH2 in two independent cohorts of sporadic breast cancers.

Methods:
Immunohistochemical evaluation of SIAH2 protein expression was conducted in normal breast tissues and in tissue microarrays comprising ductal carcinoma in situ and a cohort of invasive breast carcinomas. Correlation analysis was performed between SIAH2 and clinicopathological variables and intrinsic breast cancer subgroups and validated on a cohort of 293 invasive ductal carcinomas. Promoter methylation, gene copy number and mRNA expression of SIAH2 was determined in a panel of basal-like tumors and cell lines.

Results:

There was a significant increase in nuclear SIAH2 expression from normal breast tissues through to DCIS and progression to invasive cancers. A significant inverse correlation was apparent between SIAH2 and ER and PR and a positive association with tumor grade, HER2, p53 and intrinsic basal-like subtype. A logistic regression confirmed the significant positive association between SIAH2 expression and basal-like phenotype. No SIAH2 promoter methylation was identified, yet there was a significant correlation between SIAH2 mRNA and gene copy number. SIAH2 positive tumors were associated with a shorter relapse-free survival in a univariate but not multivariate analysis.

Conclusions:

SIAH2 expression is upregulated in basal-like breast cancers via copy number changes and/or transcriptional activation by p53 and is likely to be partly responsible for the enhanced hypoxic drive through abrogation of the prolyl hydroxylases.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 24 May 2011, 14:23:44 EST by Dr Nicola Waddell on behalf of Institute for Molecular Bioscience