EXPRESSION OF ALTERNATIVELY SPLICED LCK TRANSCRIPTS FROM THE PROXIMALPROMOTER IN COLORECTAL-CANCER DERIVED CELL-LINES

Ectopic expression of the lck gene has been demonstrated in epithelial tumor cells to be directed by the proximal promoter element. Variabil ity 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 exper iments clearly indicate that the three different types of lck transcri pts, which are exclusively derived from the proximal promoter, were ex pressed in our panel of colorectal cancer cells analyzed. DNA sequence analyses of the reversely transcribed lck mRNAs revealed that they in deed represented the lck transcripts designated type IA, IB and IC, wh ich have recently been identified in T-cells. Similarly with the situa tion in immature hematopoetic malignancies lck transcript IB steady st ate levels were predominant in colorectal cancer derived cell lines. T hese findings lend further support to the notion, that expression of l ck is part of anectopic lymphoid activation and differentiation progra m induced in these epithelial tumors.