Mutation analysis of the mel-18 gene that shows decreased expression in human breast cancer cell lines

被引：19

作者：

Matsuo F. ^{[1
,4
]}

Yano K.-I. ^{[1
]}

Saito H. ^{[1
]}

Morotomi K. ^{[1
]}

Kato M. ^{[1
]}

Yoshimoto M. ^{[2
]}

Kasumi F. ^{[2
]}

Akiyama F. ^{[3
]}

Sakamoto G. ^{[3
]}

Miki Y. ^{[1
]}

机构：

[1] Department of Molecular Diagnosis, Cancer Institute, Japanese Foundation for Cancer Research, Toshima-ku, Tokyo 170-8455

[2] Department of Breast Surgery, Cancer Institute Hospital

[3] Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research

[4] First Department of Surgery, Faculty of Medicine, Fukuoka University

来源：

Breast Cancer | 2002年 / 9卷 / 1期

关键词：

Haploinsufficiency; LOH; Mel-18; Sporadic and hereditary breast cancer; Tumor suppressor gene;

D O I：

10.1007/BF02967544

中图分类号：

学科分类号：

摘要：

Background: Mammalian mel-18 is a member of the polycomb group, and it acts as a transcriptional repressor with DNA binding activity. Murine mel-18 negatively regulates the cell cycle through the c-myc/cdc25 cascade, and mice haploinsufficient for mel-18 develop mammary gland tumors. In addition, the human homolog of mel-18 is located at 17q, on which candidate tumor suppressor genes for breast cancer have been suggested for a long time. These observations indicate that the mel-18 gene may be a tumor suppressor gene for breast cancer. To investigate this possibility, we examined the expression of mel-18 mRNA in human breast cancer cell lines and searched for mel-18 gene mutations in sporadic and familial breast cancers. Methods: The expression of mel-18 mRNA was examined in five breast cancer cell lines by RT-PCR, and somatic and germline mutations of the mel-18 gene were analyzed by the PCR-SSCP and sequence methods in 48 sporadic breast cancers, including 16 cases with loss of heterozygosity (LOH) at the mel-18 locus, and in 23 cases from 18 breast cancer families, respectively. Results: We found that most cell lines examined here showed decreased expression of mel-18 mRNA, however, no alteration other than a single nucleotide change that did not lead to amino acid alteration in one patient was identified. Conclusion: Our results reveal that mel-18 gene mutations are exceedingly rare in human breast cancers, and a reduction of mel-18 expression in human breast cancer cell lines would support a role for mel-18 haploinsufficiency in breast carcinogenesis.

引用

页码：33 / 38

页数：5

共 22 条

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