Selective Expression of Alternative lck mRNAs in Human Malignant Cell Lines

Abstract

The lck protein tyrosine kinase is normally expressed in a cell type-specific fashion, with mRNA being confined to cells of lymphoid lineage. Despite this highly specific pattern of expression in normal tissues, lck mRNA has also been detected in selected cell lines derived from human nonlymphoid neoplasms. In this study we explored the mechanisms underlying the expression of lck mRNA within human nonlymphoid neoplastic cell lines. We determined that lck mRNA expression was correlated with transcriptional activation and that there was no evidence for genomic rearrangement or amplification within the lck coding region to account for the expression of lck mRNA in the nonlymphoid neoplastic cell lines. The lck gene has previously been shown to contain two distinct promoter elements. In this study, we demonstrated that lck-producing cell lines derived from human nonlymphoid neoplasms expressed transcripts initiated exclusively from the 3′-most promoter element (3′ promoter). In contrast, lymphoid cell lines derived from nonmalignant sources expressed lek transcripts exclusively initiated from the 5′-most promoter element (5′ promoter). Most cell lines derived from human lymphoid neoplasms express lek transcripts initiated from both the 5′ and 3′ promoters in various ratios. Thus, lek expression in a variety of malignant cell lines results from a selective induction of transcription from the 3′ promoter.