A NOVEL BCL-2 RELATED GENE, BFL-1, IS OVEREXPRESSED IN STOMACH-CANCERAND PREFERENTIALLY EXPRESSED IN BONE-MARROW

Programmed cell death (apoptosis) is an active process which is geneti cally encoded and plays an important role in several cellular activiti es such as embryonic development, deletion of autoreactive T-cells and homeostasis. Several genes regulating apoptosis have been reported, i ncluding p53, one of the tumor suppressor genes, c-myc, one of the pro to-oncogenes, and various kinds of Bcl-2 related genes, A new cDNA clo ne which is homologous to Bcl-2, named as Bfl-1 were isolated from a h uman fetal liver at 22 week of gestation. This clone was identified by computer analysis of random cDNA sequences that were obtained in an e ffort to expand the expressed sequence tag (EST) databases to be used for human genome analysis. The homology was recognized by 72% amino ac id identity to the murine Al gene, a member of the Bcl-2-related genes . The homology to the BH1 and BH2 domains of Bcl-2 was especially sign ificant, suggesting that Bfl-1 is a new member of the Bcl-2-related ge nes. Bfl-1 is abundantly expressed in the bone marrow and at a low lev el in some other tissues. Interestingly, a correlation was noted betwe en the expression level of Bh-l gene and the development of stomach ca ncer in eight sets of clinical samples. It is conceivable that Bfl-1 i s involved in the promotion of the cell survival in the stomach cancer development or progression.