当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF ONCOLOGY期刊下所有文献 > Mutations in mismatch repair genes are involved in the neoplastic transformation of human breast epithelial cells.

Mutations in mismatch repair genes are involved in the neoplastic transformation of human breast epithelial cells.

Abstract：

:Mismatch repair (MMR) genes play a fundamental role in the correction of replication errors, leading to cancer development when mutated. In order to test the hypothesis that the MMR system was compromised in the initiation and progression of breast cancer, we used an in vitro-in vivo model for analyzing the mRNA levels of the MMR genes hMLH1, hMSH2, hPMS1, hPMS2 and hMSH6. MCF-10F, immortalized human breast epithelial cells, BP-1, benz(a)pyrene (BP)-transformed cells, BP-1Tras, a tumorigenic cell line derived from c-Ha-ras transfected BP-1 cells, and seven tumor-derived cell (TDC) lines obtained from BP-1Tras-induced tumors were tested. hMLH1, hMSH2, hPMS1, hPMS2 and hMSH6 mRNA expression were similar in MCF-10F, BP-1, and BP-1Tras cells; hMLH1 and hPMS1 were also equally expressed in TDC. An exception was hPMS2, whose mRNA level was decreased from BP-1Tras and from all TDC. hMSH2 and hMSH6 mRNA were also decreased in most TDC. DNA sequencing revealed mutations in hMSH2, which in MCF-10F cells had one frameshift mutation and one polymorphism in exons 12 and 13, respectively. Two mutations in exon 13, and three in exon 14 were detected in BP-1 and TDC, which had, in addition, three missense mutations in exon 14. hPMS2 had four mutations in exon 10 in MCF-10F cells, and BP-1 cells had three missense mutations in exon 9, four missense and one non-sense mutations in exon 10, codon 675 (Arg x Stop signal). BP-1Tras and TDC shared three missense mutations with BP-1 cells, and in addition had seven missense and one non-sense mutations in exon 9. hMSH6 had three frameshift and three missense mutations in exons 4 and 5 in BP-1, and 12 mutations in the same exons in BP-1Tras and TDC, which had three additional mutations in exons 4 and 5. This is the first report demonstrating mutations of MMR genes during the neoplastic transformation of human breast epithelial cells.

journal_name

Int J Oncol

journal_title

International journal of oncology

authors

Balogh GA,Russo IH,Russo J

keywords:

subject

Has Abstract

pub_date

2003-08-01 00:00:00

pages

411-9

issue

eissn

1019-6439

issn

1791-2423

journal_volume

pub_type

杂志文章

在线工具

Mutations in mismatch repair genes are involved in the neoplastic transformation of human breast epithelial cells.