An alternative pathway for expression of p56^lck from type I promoter transcripts in colon carcinoma

Abstract

The lymphoid-specific protein tyrosine kinase, p56^lck which is essential for both T cell development and function, is aberrantly expressed in colon and small lung carcinoma lines. In this paper, we demonstrate p56^lck is also expressed in colon tumour biopsies due predominantly 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- and Myb-related transcription factors. In contrast, in colon tumour lines 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 for binding and activating the lck type I promoter in colon carcinoma cells. Co-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 aberrant expression of p56^lck from the lck type I promoter in colon carcinoma arises from transcriptional activation mediated by Ets- and HMG-related transcription factors.