Lose Felicity, Arnold Jeremy, Young David B, Brown Carolyn J, Mann Graham J, Pupo Gulietta M, Khanna Kum Kum, Chenevix-Trench Georgia, Spurdle Amanda B
Cancer and Cell Biology Division, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, Queensland, Australia, 4006.
Breast Cancer Res. 2007;9(4):R54. doi: 10.1186/bcr1759.
BRCA1 is involved in numerous essential processes in the cell, and the effects of BRCA1 dysfunction in breast cancer carcinogenesis are well described. Many of the breast cancer susceptibility genes such as BRCA2, p53, ATM, CHEK2, and BRIP1 encode proteins that interact with BRCA1. BCL6 corepressor-like 1 (BCoR-L1) is a newly described BRCA1-interacting protein that displays high homology to several proteins known to be involved in the fundamental processes of DNA damage repair and transcription regulation. BCoR-L1 has been shown to play a role in transcription corepression, and expression of the X-linked BCoR-L1 gene has been reported to be dysregulated in breast cancer subjects. BCoR-L1 is located on the X chromosome and is subject to X inactivation.
We performed mutation analysis of 38 BRCA1/2 mutation-negative breast cancer families with male breast cancer, prostate cancer, and/or haplotype sharing around BCoR-L1 to determine whether there is a role for BCoR-L1 as a high-risk breast cancer predisposition gene. In addition, we conducted quantitative real-time PCR (qRT-PCR) on lymphoblastoid cell lines (LCLs) from the index cases from these families and a number of cancer cell lines to assess the role of BCoR-L1 dysregulation in cancer and cancer families.
Very little variation was detected in the coding region, and qRT-PCR analysis revealed that BCoR-L1 expression is highly variable in cancer-free subjects, high-risk breast cancer patients, and cancer cell lines. We also report the investigation of a new expression control, DIDO1 (death inducer-obliterator 1), that is superior to GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and UBC (ubiquitin C) for analysis of expression in LCLs.
Our results suggest that BCoR-L1 expression does not play a large role in predisposition to familial breast cancer.
BRCA1参与细胞内众多重要过程，BRCA1功能障碍在乳腺癌致癌过程中的影响已得到充分描述。许多乳腺癌易感基因，如BRCA2、p53、ATM、CHEK2和BRIP1，编码与BRCA1相互作用的蛋白质。BCL6共抑制因子样1（BCoR-L1）是一种新描述的与BRCA1相互作用的蛋白质，与已知参与DNA损伤修复和转录调控基本过程的几种蛋白质具有高度同源性。BCoR-L1已被证明在转录共抑制中发挥作用，并且据报道，X连锁的BCoR-L1基因在乳腺癌患者中表达失调。BCoR-L1位于X染色体上，会发生X染色体失活。
我们对38个BRCA1/2突变阴性的乳腺癌家族进行了突变分析，这些家族患有男性乳腺癌、前列腺癌和/或在BCoR-L1周围存在单倍型共享，以确定BCoR-L1作为高危乳腺癌易感基因是否起作用。此外，我们对这些家族的先证者的淋巴母细胞系（LCL）和一些癌细胞系进行了定量实时PCR（qRT-PCR），以评估BCoR-L1表达失调在癌症和癌症家族中的作用。
在编码区检测到的变异非常少，qRT-PCR分析表明，BCoR-L1在无癌受试者、高危乳腺癌患者和癌细胞系中的表达高度可变。我们还报告了对一种新的表达对照DIDO1（死亡诱导消除因子1）的研究，它在分析LCL中的表达方面优于甘油醛-3-磷酸脱氢酶（GAPDH）和泛素C（UBC）。
我们的结果表明，BCoR-L1表达在家族性乳腺癌易感性中不起主要作用。
