Differential Expression of the Human Calcitonin — CGRP Gene in Medullary Thyroid Carcinoma and Lung Carcinoma Cell Lines

Abstract

The application of molecular techniques has provided new insight into the structure and expression of peptide hormone genes (Craig and Hall 1983). Application of this technology to the study of calcitonin gene expression has proved particularly intriguing. Studies on the structure and expression of the rat calcitonin gene have demonstrated the generation by RNA processing of alternative mRNA species in an apparently tissue-specific manner (Amara et al. 1982). Each mRNA encodes a polyprotein subsequently cleaved and modified by enzymes within the secretory pathway to yield calcitonin or the calcitonin gene-related peptide (CGRP). The application of immunocytochemical techniques using antiserum raised against a synthetic fragment of rat CGRP demonstrates a wide distribution of CGRP-producing cells and points to a possible role as a neurotransmitter or neuromodulator molecule (Rosenfeld et al. 1983). In man, calcitonin is synthesized normally at low levels by C cells of the thyroid (Austin and Heath 1981), though at elevated levels ectopically by lung carcinoma (Coombes et al. 1974) and at grossly elevated levels eutopically in medullary thyroid carcinoma (Milhaud et al. 1974). In common with rat, differential expression of the human calcitonin gene also results in the expression of two different mRNA species encoding polyproteins, proteolytically cleaved within the secretory pathway to produce biologically active peptides, calcitonin, or CGRP (Craig et al. 1982; Edbrooke et al. 1985).