Edbrooke M R, Parker D, McVey J H, Riley J H, Sorenson G D, Pettengill O S, Craig R K
EMBO J. 1985 Mar;4(3):715-24. doi: 10.1002/j.1460-2075.1985.tb03688.x.
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 hybridisation probes specific to calcitonin mRNA, intron, coding and non-coding regions of the CGRP mRNA, we demonstrate by Southern blotting the existence of a second human CGRP gene, and by RNA blotting and S1 mapping, the differential expression of calcitonin and CGRP in medullary thyroid carcinoma and human lung tumour 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 antisera 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 tumour cell-lines. These studies indicate that CGRP is a tumour marker of diagnostic and possibly prognostic value in the management of lung and thyroid tumours.
对部分加工的聚腺苷酸化前体RNA转录本进行的核苷酸序列分析表明，人类降钙素基因与大鼠降钙素基因一样，编码降钙素和降钙素基因相关肽（CGRP）。使用针对降钙素mRNA、CGRP mRNA的内含子、编码区和非编码区的杂交探针，我们通过Southern印迹证明了人类第二个CGRP基因的存在，并通过RNA印迹和S1作图证明了降钙素和CGRP在甲状腺髓样癌和人肺肿瘤细胞系中的差异表达。这些研究表明，从单个基因差异表达降钙素和CGRP需要单独的转录后事件，优先使用剪接受体位点来合成CGRP mRNA，以及由反式作用基因产物调节转录后切割来合成降钙素mRNA。使用针对CGRP和降钙素产生的抗血清进行的研究表明，甲状腺髓样癌患者血浆中CGRP的循环水平升高，与降钙素水平不平行，并且肺肿瘤细胞系的分泌物中存在CGRP。这些研究表明，CGRP是一种在肺癌和甲状腺肿瘤管理中具有诊断和可能预后价值的肿瘤标志物。
