AN ALTERNATIVE PATHWAY FOR EXPRESSION OF P56(LCK) FROM TYPE-I PROMOTER TRANSCRIPTS IN COLON-CARCINOMA

The lymphoid-specific protein tyrosine kinase, p56(lck) which is essen tial for both T cell development and function, is aberrantly expressed in colon and small lung carcinoma lines, In this paper, we demonstrat e p56(lck) is also expressed in colon tumour biopsies due predominantl y or exclusively to the use of the lck type I promoter, In T leukaemia lines, the lck type I promoter requires binding sites for both Ets- a nd Myb-related transcription factors, In contrast, in colon tumour lin es the activation of the lck type I promoter requires the Ets but not the Myb binding site, In these lines, a consensus binding site for HMG -related transcription factors, AACAAAG, is required for efficient lck type I promoter activity, Sox-4 is a candidate transcription factor f or binding and activating the lck type I promoter in colon carcinoma c ells. Go-expression of Ets-1 and Sox-4, but neither protein alone, was sufficient to activate the lck type I promoter in HeLa cells which do not normally express lck transcripts, These results suggest that aber rant expression of p56(lck) from the lck type I promoter in colon carc inoma arises from transcriptional activation mediated by Ets-and HMG-r elated transcription factors.