Taxanes are among the most active agents and they are now known to be an indispensable component in chemotherapy for breast
cancer. However, some patients are resistant to taxanes and the identification of the molecular characteristics that can predict
the sensitivity to taxanes would be useful in selecting the most appropriate patients to receive taxane therapy. Taxanes are
antimicrotubular agents that promote microtubular assembly and stabilize microtubules by preventing depolymerization. They
interfere with normal mitotic transition and causes cell cycle arrest in the G2-M metaphase.
CHFR (checkpoint with forkhead-associated and ring finger) is a recently identified gene, which functions as an important checkpoint
protein early in G2-M transition. Its activation delays the cell cycle in prophase and promotes cell survival in response
to the mitotic stress induced by either nocodazole or taxane. CHFR is frequently downregulated in human cancers, mostly owing
to the hypermethylation of its promoter region. CHFR downregulation has been found in primary cancers or in the established
tumor cells of various origins, such as the lung, colon, esophagus, and stomach. The aberrant hypermethylation of
CHFR promoter appears to be a good molecular marker to predict sensitivity to taxanes in gastric, lung, and colon cancer. A downregulation
of CHFR was observed in breast cancer cells, however, no apparent promoter hypermethylation has yet been reported. In addition,
an alteration of the CHFR expression or aberrant promoter hypermethylation in primary breast cancer has not been fully investigated.
In this study, we examined the methylation status of the promoter region of
CHFR gene in 110 primary breast cancers. We observed the hypermethylation of the
CHFR promoter region in only one case (0.9%). We herein show that the aberrant hypermethylation of this region is quite a rare
event in primary breast carcinoma.
Keywords aberrant hypermethylation - breast cancer - CFHR - methylation-specific PCR - taxane