Limited up-regulation of DNA methyltransferase in human colon cancer reflecting increased cell proliferation

摘要: Epigenetic alterations in the genome of tumor cells have attracted considerable attention since discovery widespread DNA methylation colorectal cancers over 10 years ago. However, mechanism these changes has remained obscure. el-Deiry and coworkers [el-Deiry, W. S., Nelkin, B. D., Celano, P., Yen, R. C., Falco, J. Hamilton, S. & Baylin, (1991) Proc. Natl. Acad. Sci. USA 88, 3470-3474], using a quantitative reverse transcription-PCR assay, reported 15-fold increased expression methyltransferase (MTase) colon cancer, compared with matched normal mucosa, 200-fold increase MTase mRNA levels mucosa unaffected patients. These authors suggested that increases play direct pathogenetic role carcinogenesis. To test this hypothesis, we developed sensitive RNase protection assay MTase, linear three orders magnitude. Using on 12 carcinomas mucosal specimens, observed 1.8- to 2.5-fold carcinoma from same There was no significant difference between affected Furthermore, when normalized histone H4 expression, measure S-phase-specific moderate longer observed. data are contrast previously results, they indicate cancer nonspecific compatible other markers cell proliferation.