Expression profiles of BRCA1 splice variants in asynchronous and in G1/S synchronized tumor cell lines

Expression profiles of BRCA1 splice variants in asynchronous and in G1/S synchronized tumor cell lines
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DOI:
10.1006/bbrc.2000.4068
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发表时间:
2001-01-12
影响因子:
3.1
通讯作者:
Olah, E
Olah, E
中科院分区:
生物学4区
文献类型:
--
作者:
Orban, TI;Olah, E

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在散发性乳腺癌/卵巢癌病例中,怀疑通过生殖系突变以外的机制破坏BRCA 1基因的功能。使用核糖核酸酶保护试验和多重RT-PCR,我们研究了总BRCA 1 mRNA池的变化和四个主要的BRCA 1剪接变异体的表达谱在异步和G1/S同步肿瘤细胞群体相比,正常乳腺细胞。在MCF-7和MDA-MB-231乳腺癌、OVCAR-5卵巢癌和K562白血病细胞系上进行实验。与白血病细胞系相比,在所检查的乳腺和卵巢肿瘤细胞系中,全长、Delta(11 q)、Delta(9,10)和Delta(9,10,11 q)BRCA 1亚型的比例显示出不同的表达模式。这一观察结果提出了一种可能性,即BRCA 1基因选择性剪接的失调可能参与乳腺和卵巢肿瘤的形成,即使在没有生殖系突变的情况下。(C)北京:科学出版社.
Disrupting the function of the BRCA1 gene by mechanisms other than germline mutations is suspected to occur in cases of sporadic breast/ovarian cancers. Using ribonuclease protection assay and multiplex RT-PCR, we examined the change of the total BRCA1 mRNA pool and the expression profile of four predominant BRCA1 splice variants in asynchronous and in G1/S synchronized tumor cell populations compared to normal breast cells. Experiments were carried out on MCF-7 and MDA-MB-231 breast cancer, OVCAR-5 ovarian cancer, and K562 leukemia cell lines. The ratio of the full length, the Delta (11q), the Delta (9,10), and the Delta (9,10,11q) BRCA1 isoforms showed different expression patterns in the examined breast and ovarian tumor cell lines as compared to the leukemia cell line. This observation raises the possibility that the dysregulation of alternative splicing of the BRCA1 gene could be involved in tumor formation in the breast and the ovary, even in the absence of germline mutations. (C) 2001 Academic Press.