Apoptosis inhibiting factor Bcl-x(L) might be the crucial member of the Bcl-2 gene family in colorectal cancer

Since the role of the Bcl-2 gene family has been only poorly investigated i n colorectal cancer, we have examined the expression of the apoptosis block ers Bcl-x(L) and Bcl-2, as well as the proapoptotic factors Bax and Bak. No rthern blot analysis and immunohistochemistry were performed on normal and cancerous colonic tissue from 12 patients. In colorectal cancer, Bcl-x(L) i mmunoreaction was stronger than in normal controls, and 83% of the cancers had increased Bcl-x(L) mRNA expression. The median densitometric Bcl-x(L) v alues were 3.4-fold higher in carcinomas (P < 0.005). In contrast to the no rmal colon, colorectal carcinomas often lack any Bcl-2 immunostaining, and Eel-2 mRNA was not detectable by Northern blots either. Bar was not obvious ly altered in colorectal cancer, either at the protein level or at the mRNA level compared to the normal control colon. Bak mRNA expression exhibited a wide variation in carcinomas, but was somewhat decreased in comparison to the controls. Of these members of the Eel-2 gene family, Bcl-x(L) seems to play a major role in colorectal tumori genesis and disease progression. An agonistic effect might have caused the tendency for reduced Bak expression . The Bcl-2/Bax regulation system of cell homeostasis seems to be of lesser importance.