Expression of the Ca2+-Activated chloride channel genes CLCA1 and CLCA2 isdownregulated in human colorectal cancer

The role of ion channels in carcinogenesis and tumor progression remains un clear. We have used suppression subtractive hybridization of mRNA from pair ed normal colon epithelium and tumor, followed by quantitative kinetic RT-P CR, to demonstrate that the transcription of two members of a novel Ca2+-de pendent chloride channel family, CLCA1 and CLCA2, was significantly downreg ulated in approximately 80% of colorectal carcinomas. This figure rose to > 90% when expression was adjusted for tumor cell proliferation. In normal co lon epithelium, CLCA1 mRNA levels were significantly associated with c-myc transcription but became decoupled in the tumor samples. There was no assoc iation between CLCA2 and either CLCA1 or c-myc mRNA levels. Transcription o f both genes in three colorectal cancer cell lines, T84, HT29, and Caco2, w as barely detectable. Illegitimate transcription of CLCA1 was detected in 1 2 of 15 blood samples taken from healthy volunteers, making its use as a ma rker for the detection of tumor spread unreliable. Our results suggest that CLCA1 could specify a new tumor suppressor and that, as in breast cancer, CLCA2 may function as a tumor suppressor in colorectal cancer.