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Expression of the human calcitonin calcitonin gene related peptide gene in lung and thyroid carcinoma


, : Expression of the human calcitonin calcitonin gene related peptide gene in lung and thyroid carcinoma. EMBO (European Molecular Biology Organization) Journal 4(3): 715-724

Nucleotide sequence analysis of a partially processed polyadenylated precursor RNA transcript shows that the human calcitonin gene in common with the rat calcitonin gene, encodes calcitonin and the calcitonin gene related peptide (CGRP). Using hybridization probes specific to calcitonin mRNA, intron, coding and non-coding regions of the CGRP mRNA, Southern blotting demonstrates the existence of a 2nd human CGRP gene, and by RNA blotting and S1 mapping, the differential expression of calcitonin and CGRP in medullary thyroid carcinoma and human lung tumor cell-lines. These studies implicate the requirement for separate post-transcriptional events in the differential expression of calcitonin and CGRP from a single gene, the preferential use of splice acceptor sites for the synthesis of CGRP mRNA, and post-transcriptional cleavage modulated by a trans-acting gene product for the synthesis of calcitonin mRNA. Studies using antiserum raised against CGRP and calcitonin, demonstrate elevated circulating levels of plasma CGRP in medullary thyroid carcinoma which do not parallel calcitonin levels, and the presence of CGRP in secretions from lung tumor cell-lines. Evidently CGRP is a tumor marker of diagnostic and possibly prognostic value in the management of lung and thyroid tumors.

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