Matsuo Fumie, Yano Ken-ichi, Saito Hiroko, Morotomi Keiko, Kato Masahiro, Yoshimoto Masataka, Kasumi Fujio, Akiyama Futoshi, Sakamoto Goi, Miki Yoshio
Department of Molecular Diagnosis, Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
Breast Cancer. 2002;9(1):33-8. doi: 10.1007/BF02967544.
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.
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.
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.
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.
