Expression of alternatively spliced lck transcripts from the proximal promoter in colorectal cancer derived cell...

Ectopic expression of the lck gene has been demonstrated in epithelial tumor cells to be directed by the proximal promoter element. Variability of lck transcripts at the 5' end detected in T-cells and lymphoid malignancies prompted us to investigate the potential heterogeneity of lck mRNA molecules in colorectal cancer derived cell lines. Our experiments clearly indicate that the three different types of lck transcripts, which are exclusively derived from the proximal promoter, were expressed in our panel of colorectal cancer cells analyzed. DNA sequence analyses of the reversely transcribed lck mRNAs revealed that they indeed represented the lck transcripts designated type 1A, 1B and 1C, which have recently been identified in T-cells. Similarly with the situation in immature hematopoietic malignancies lck transcript 1B steady state levels were predominant in colorectal cancer derived cell lines. These findings lend further support to the notion, that expression of lck is part of anectopic lymphoid activation and differentiation program induced in these epithelial tumors.