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 isoform-specific mRNA expression in tumor and nontumor tissues from patients with breast cancer.
We thank the Shared Resources at Albert Einstein College of Medicine: Molecular Cytogenetic, in particular, Dr. Jidong Shan and Dr. Yinghui Song for help with the FISH analysis. The work of the authors was supported by grants from the ACS (ACS RSG-11-021-01-CNE to C.M.); C.M. is supported by the CCSG P30CA013330.
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