Expression of the gastrin-releasing peptide gene in human small cell lung cancer. Evidence for alternative processing resulting in three distinct mRNAs.

cDNA clones to human prepro-gastrin-releasing peptide (prepro-GRP) mRNA detect synthesis of prepro-GRP-related transcripts in 4 of 7 small cell lung cancer (SCLC) cell lines and 1 of 2 metastatic SCLC tumors examined. A correlation is noted between prepro-GRP gene expression and the occurrence of bombesin-related immunoreactivity in SCLC cell lines. Examination of the structure of prepro-GRP transcripts found in SCLC reveals three types of prepro-GRP mRNA which differ in the structure of a putative GRP-associated peptide in the pro-GRP precursor. The subcellular distribution of prepro-GRP-related RNAs and structure of SCLC-derived prepro-GRP cDNA clones suggest that all three types of transcript could function as mRNAs, although there are differences in the prevalence of the different RNA types in different cellular compartments. Comparison of the sequence of cDNA clones with the sequence of a genomic prepro-GRP clone reveals that the three forms of prepro-GRP mRNA arise from a single primary transcript which undergoes alternative processing from two splice donor sites to two splice acceptor sites. The predicted amino acid sequence of the translated products of the three mRNAs are quite distinct, leading to predicted pro-GRP molecules of differing structure.