Implication of snoRNA U50 in human breast cancer.
Implication of snoRNA U50 in human breast cancer.
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DOI：
10.1016/s1673-8527(08)60134-4
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发表时间：
2009-08
影响因子：
5.9
通讯作者：
Dong, Jin-Tang
中科院分区：
文献类型：
--
作者：
Dong, Xue-Yuan;Guo, Peng;Boyd, Jeff;Sun, Xiaodong;Li, Qunna;Zhou, Wei;Dong, Jin-Tang
6q染色体缺失在乳腺癌中很常见，且缺失常涉及6q14-q16区域。然而目前，潜在的抑癌基因尚未确定。根据最近的一项研究，将 snoRNA U50 确定为前列腺癌 6q14-16 肿瘤抑制基因的候选基因，我们研究了 U50 是否也与乳腺癌有关。基于 PCR 的方法表明，U50 在乳腺癌细胞系中频繁发生基因组缺失和转录下调。突变筛查在细胞系和乳腺癌原发肿瘤中发现了与前列腺癌相同的 U50 2-bp 缺失，并且该缺失既发生在体细胞中，又发生在种系中。对一组乳腺癌病例和对照突变的基因分型表明，虽然该突变的纯合基因型很少见，但其杂合基因型在乳腺癌女性中更常见。从功能上讲，U50 的重新表达导致乳腺癌细胞系中集落形成的抑制。这些结果表明非编码 snoRNA U50 在乳腺癌的发生和/或进展中发挥作用。
Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q14-q16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent study identifying snoRNA U50 as a candidate for the 6q14-16 tumor suppressor gene in prostate cancer, we investigated whether U50 is also involved in breast cancer. PCR-based approaches showed that U50 underwent frequent genomic deletion and transcriptional downregulation in cell lines derived from breast cancer. Mutation screening identified the same 2-bp deletion of U50 as in prostate cancer in both cell lines and primary tumors from breast cancer, and the deletion was both somatic and in germline. Genotyping of a cohort of breast cancer cases and controls for the mutation demonstrated that, while homozygous genotype of the mutation was rare, its heterozygous genotype occurred more frequently in women with breast cancer. Functionally, re-expression of U50 resulted in the inhibition of colony formation in breast cancer cell lines. These results suggest that noncoding snoRNA U50 plays a role in the development and/or progression of breast cancer.