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Breast Cancer Research
Published in: Breast Cancer Research 4/2011

Open Access 01-08-2011 | Research article

Septin 9 isoform expression, localization and epigenetic changes during human and mouse breast cancer progression

Authors: Diana Connolly, Zhixia Yang, Maria Castaldi, Nichelle Simmons, Maja H Oktay, Salvatore Coniglio, Melissa J Fazzari, Pascal Verdier-Pinard, Cristina Montagna

Published in: Breast Cancer Research | Issue 4/2011

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Abstract

Introduction

Altered expression of Septin 9 (SEPT9), a septin coding for multiple isoform variants, has been observed in several carcinomas, including colorectal, head and neck, ovarian and breast, compared to normal tissues. The mechanisms regulating its expression during tumor initiation and progression in vivo and the oncogenic function of its different isoforms remain elusive.

Methods

Using an integrative approach, we investigated SEPT9 at the genetic, epigenetic, mRNA and protein levels in breast cancer. We analyzed a panel of breast cancer cell lines, human primary tumors and corresponding tumor-free areas, normal breast tissues from reduction mammoplasty patients, as well as primary mammary gland adenocarcinomas derived from the polyoma virus middle T antigen, or PyMT, mouse model. MCF7 clones expressing individual GFP-tagged SEPT9 isoforms were used to determine their respective intracellular distributions and effects on cell migration.

Results

An overall increase in gene amplification and altered expression of SEPT9 were observed during breast tumorigenesis. We identified an intragenic alternative promoter at which methylation regulates SEPT9_v3 expression. Transfection of specific GFP-SEPT9 isoforms in MCF7 cells indicates that these isoforms exhibit differential localization and affect migration rates. Additionally, the loss of an uncharacterized SEPT9 nucleolar localization is observed during tumorigenesis.

Conclusions

In this study, we found conserved in vivo changes of SEPT9 gene amplification and overexpression during human and mouse breast tumorigenesis. We show that DNA methylation is a prominent mechanism responsible for regulating differential SEPT9 isoform expression and that breast tumor samples exhibit distinctive SEPT9 intracellular localization. Together, these findings support the significance of SEPT9 as a promising tool in breast cancer detection and further emphasize the importance of analyzing and targeting SEPT9 isoform-specific expression and function.
Appendix
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Metadata
Title
Septin 9 isoform expression, localization and epigenetic changes during human and mouse breast cancer progression
Authors
Diana Connolly
Zhixia Yang
Maria Castaldi
Nichelle Simmons
Maja H Oktay
Salvatore Coniglio
Melissa J Fazzari
Pascal Verdier-Pinard
Cristina Montagna
Publication date
01-08-2011
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2011
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2924

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