Analysis of the candidate 8p21 tumour suppressor, BNIP3L, in breast and ovarian cancer.
Analysis of the candidate 8p21 tumour suppressor, BNIP3L, in breast and ovarian cancer.
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DOI：
10.1038/sj.bjc.6600674
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发表时间：
2003-01-27
影响因子：
8.8
通讯作者：
Arnold J
中科院分区：
文献类型：
--
作者：
Lai J;Flanagan J;Phillips WA;Chenevix-Trench G;Arnold J
8 号染色体短臂 8p12-p23 杂合性丢失 (LOH) 是乳腺癌和卵巢癌中最常见的遗传事件之一，表明存在共同的抑癌基因。微细胞介导的 8 号染色体染色体转移可抑制结直肠癌细胞系和前列腺癌细胞系的致瘤性和生长，进一步支持 8p 上存在肿瘤抑制基因。我们采用候选基因方法来尝试鉴定位于 8p12-p23 的肿瘤抑制基因。 BNIP3L 与促凋亡蛋白具有序列同源性，并且能够抑制软琼脂中的集落形成，其位于 8p21，位于卵巢癌 LOH、乳腺癌 LOH 和前列腺癌转移抑制的区域内。通过 RT-PCR 和 Northern blot 分析对乳腺癌和卵巢癌细胞系中的 BNIP3L 表达进行了评估，发现其表达水平与各自正常上皮细胞系中的表达水平相似。对 40 个原发性卵巢肿瘤和 25 个原发性乳腺肿瘤中的 BNIP3L 进行遗传分析，确定了一种卵巢肿瘤中的一种体细胞内含子突变，以及多种多态性，其中包括一种导致氨基酸取代的多态性。这些数据表明 BNIP3L 不太可能是卵巢癌或乳腺癌中 8p LOH 的靶标。
Loss of heterozygosity (LOH) on the short arm of chromosome 8, at 8p12–p23, is one of the most frequent genetic events in both breast and ovarian cancer, suggesting the location of a shared tumour suppressor gene. Microcell-mediated chromosome transfer of chromosome 8 suppresses tumorigenicity and growth of colorectal and prostate cancer cell lines, further supporting the presence of a tumour suppressor gene on 8p. We have taken a candidate gene approach to try to identify this tumour suppressor gene at 8p12–p23. BNIP3L, which has sequence homology to pro-apoptotic proteins and the ability to suppress colony formation in soft agar, is located at 8p21, within a region of ovarian cancer LOH, breast cancer LOH and prostate cancer metastasis suppression. BNIP3L expression was assessed by both RT–PCR and Northern blot analysis in breast and ovarian cancer cell lines and found to be expressed at similar levels relative to expression in their respective normal epithelial cell lines. Genetic analysis of BNIP3L in 40 primary ovarian and 25 primary breast tumours identified one somatic, intronic mutation in one ovarian tumour, as well as several polymorphisms, including one resulting in an amino-acid substitution. These data suggest that BNIP3L is unlikely to be the target of 8p LOH in ovarian or breast cancer.
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影响因子：
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作者：
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通讯作者：
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