EXPRESSION FROM THE PROXIMAL PROMOTER OF THE CARBONIC ANHYDRASE-1 GENE AS A MARKER FOR DIFFERENTIATION IN COLON EPITHELIA

Carbonic anhydrase 1 (CA1) catalyses the reversible hydration of CO2 a nd is important for cellular diffusion of CO2, ion transport and pH re gulation. The gene encoding CA1 (CA1) has two promoters. In adult colo n epithelia the proximal promoter determines high levels of expression and the distal erythroid promoter is repressed. RNA in situ hybridisa tion shows that CA1 mRNA is abundant in differentiating cells of the c olonic crypt as they migrate to the luminal surface, but is not presen t at the base of the crypts and levels are low on the luminal surface. It is likely that CA1 gene expression in these cells is regulated by differential transcription and/or mRNA stability. In contrast CA1 prot ein is localised predominantly on the luminal surface. Since CA1 mRNA and protein do not exactly co-localise it can be inferred that CA1 exp ression is also subject to post-transcriptional control. CA1 mRNA is s ignificantly reduced in colon carcinoma and in adenomas from familial adenomatous polyposis patients. Loss of CA1 expression is associated w ith the disappearance of differentiated epithelial cells. Out of twelv e colon carcinoma cell lines three, LIM1215, LIM1899 and HT115, expres sed CA1 and nine did not. This variation in expression may also be ass ociated with cell type differentiation.