Septin 9 amplification and isoform-specific expression in peritumoral and tumor breast tissue

Diana Connolly, Hien G. Hoang, Esther Adler, Cagdas Tazearslan, Nichelle Simmons, Vahni Vishala Bernard, Maria Castaldi, Maja H. Oktay, Cristina Montagna

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Septins are a large family of GTP-binding proteins abnormally expressed in many solid tumors. Septin 9 (SEPT9) in particular has been found overexpressed in diverse human tumors including breast, head and neck, ovarian, endometrial, kidney, and pancreatic cancer. Although we previously reported SEPT9 amplification in breast cancer, we now show specifically that high-grade breast carcinomas, the subtype with worst clinical outcome, exhibit a significant increase in SEPT9 copy number when compared with other tumor grades. We also present, for the first time, a sensitive and quantitative measure of seven (SEPT9-v1 through SEPT9-v7) isoform variant mRNA levels in mammary epithelial cells. SEPT9- v1, SEPT9-v3, SEPT9-v6, and SEPT9-v7 isoforms were expressed at the highest levels followed by SEPT9-v2 and SEPT9-v5, whereas SEPT9-v4 was almost undetectable. Although most of the isoforms were upregulated in primary tumor tissues relative to the patient-matched peritumoral tissues, SEPT9-v4 remained the lowest expressing isoform. This comprehensive analysis of SEPT9 provides substantial evidence for increased SEPT9 expression as a consequence of genomic amplification and is the first study to profile SEPT9-v1 through SEPT9-v7 isoformspecific mRNA expression in tumor and nontumor tissues from patients with breast cancer.

Original languageEnglish (US)
Pages (from-to)157-167
Number of pages11
JournalBiological Chemistry
Volume395
Issue number2
DOIs
StatePublished - Feb 1 2014

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Keywords

  • Amplification
  • Breast cancer
  • Expression
  • Isoforms
  • Oncogene
  • Septin 9
  • Septins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Connolly, D., Hoang, H. G., Adler, E., Tazearslan, C., Simmons, N., Bernard, V. V., Castaldi, M., Oktay, M. H., & Montagna, C. (2014). Septin 9 amplification and isoform-specific expression in peritumoral and tumor breast tissue. Biological Chemistry, 395(2), 157-167. https://doi.org/10.1515/hsz-2013-0247