Septin 9 amplification and isoform-specific expression in peritumoral and tumor breast tissue
Septin 9 amplification and isoform-specific expression in peritumoral and tumor breast tissue
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DOI：
10.1515/hsz-2013-0247
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发表时间：
2014-02-01
影响因子：
3.7
通讯作者：
Montagna, Cristina
中科院分区：
文献类型：
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作者：
Connolly, Diana;Hoang, Hien G.;Montagna, Cristina
Septins是在许多实体瘤中异常表达的GTP结合蛋白的大家族。特别地，已经发现Septin 9（SEPT9）在多种人类肿瘤中过表达，包括乳腺癌、头颈癌、卵巢癌、子宫内膜癌、肾癌和胰腺癌。尽管我们之前报道了乳腺癌中的SEPT 9扩增，但我们现在特别表明，与其他肿瘤级别相比，高级别乳腺癌（临床结果最差的亚型）的SEPT 9拷贝数显着增加。我们还提出了，第一次，一个敏感的和定量的措施七（SEPT9_v1通过SEPT9_v7）异构体变体的mRNA水平在乳腺上皮细胞。SEPT9_v1、SEPT9_v3、SEPT9_v6和SEPT9_v7同种型以最高水平表达，其次是SEPT9_v2和SEPT9_v5，而SEPT9_v4几乎检测不到。尽管相对于患者匹配的瘤周组织，大多数同种型在原发性肿瘤组织中上调，但SEPT9_v4仍然是表达最低的同种型。SEPT9的这种全面分析提供了大量证据，证明SEPT9表达增加是基因组扩增的结果，并且是第一项研究，以分析SEPT9_v1至SEPT9_v7亚型特异性mRNA在乳腺癌患者的肿瘤和非肿瘤组织中的表达。
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.