Increased expression of T‐fimbrin gene after DNA damage in CHO cells and inactivation of T‐fimbrin by CpG methylation in human colorectal cancer cells

When DNA damage is induced by unprogrammed extrinsic events, activating‐cell‐cycle checkpoints delay cell‐cycle progression in the G1 or G2 phases and allow repair of a damaged template. In this study, we evaluated changes in gene expression upon radiation‐induced G2 cell‐cycle arrest using Chinese hamster ovary (CHO) cells. T‐fimbrin, an actin‐binding protein, was overexpressed in CHO cells in which G2 arrest had been induced by X‐radiation. Northern blot analysis revealed that T‐fimbrin gene expression was induced not only by X‐radiation but also by a topoisomerase II inhibitor, etoposide. Transfection of CHO cells with a vector encoding T‐fimbrin antisense RNA demonstrated that reduced T‐fimbrin expression induced alterations in cell‐cycle control; radiation‐induced G2 arrest was short and decreased in cells transfected with antisense T‐fimbrin. Additionally, T‐fimbrin gene expression was suppressed in a human colorectal cancer cell line, SW948, because of promoter‐specific DNA methylation. These results suggest that downregulation of T‐fimbrin may be involved in cancer development through G2/M cell‐cycle control in mammalian cells. © 2002 Wiley‐Liss, Inc.