Calcitonin receptor polymorphism-function and diseases-

降钙素受体有三种同种异构体。第一类（1型）在大鼠中有465个氨基酸，在猪中有468个氨基酸。第二种类型（2型）在第二细胞外结构域有39个氨基酸插入。第三型（3型）在第一胞内结构域有16个氨基酸插入。从人卵巢癌细胞系中分离到的人CTR属于3型。利用与人CTR cDNA序列对应的引物RT-PCR技术，分析了CTR转录本在7种人肿瘤细胞系和手术标本中的表达情况。在所有样品中均发现CTR m-RNA。检测到比3型短48bp的转录本，但未检测到2型和3型的转录本。由于这种CTR的结构与1型相同，我们将其称为人类1型CTR。以人类基因组DNA为模板进行PCR研究，发现48bp序列构成一个外显子。这些结果表明，1型和3型人类CTR是由选择性剪接产生的，并且大多数人类CTR转录本是1型。对10个培养的人肿瘤细胞系和117个人血液样本的ctr进行结构分析，发现细胞内结构域4第1377个核苷酸的等位基因变异，表达脯氨酸或亮氨酸为第463个氨基酸。在日本人群中，具有脯氨酸位点的变异是更为普遍的CTR类型。我们比较了46例乳腺癌患者和50例对照患者的降钙素受体（CTR）基因的等位基因频率。CTR基因等位基因频率在两组间无显著差异。浸润性乳腺癌的CTR等位基因频率在组织学上无显著相关性。这些结果表明，CTR基因的等位变异不是日本乳腺癌发生的重要危险因素。CT或CTR在乳腺组织中的作用有待进一步研究。

There are three isoforms of calcitonin receptors (CTRs). The first type (type 1) has 465 amino acids in rat and 468 amino acids in porcine. The second type (type 2) has a 39 amino acid insertion in the second extracellular domain. The third type (type 3) has a 16 amino acid insertion in the first intracellular domain. The human CTR which has been isolated from a human ovarian carcinoma cell line belongs to this type 3.Using RT-PCR with primers whose sequences correspond to the human CTR cDNA,we analyzed the expression of the CTR transcripts in seven human tumor cell lines and surgical specimens. The CTR m-RNA were found in all samples. Transcripts which were 48bp shorter than that of the type 3 were detected, but not transcripts of type 2 and type 3. Since the structure of this CTR is same as that of the type 1, we termed it the human type 1 CTR.PCR studies using human genomic DNA as a template recvealed that the 48bp sequence constitutes an exon. These results indicate that the type 1 and the type 3 human CTRs are generated by alternative splicing and a majority of human CTR transcripts is type 1.Structural analysis of CTRs from ten cultured human tumor cell lines and 117 human blood samples demonstrated allelic variants at the 1377th nucleotide in the intracellular domain 4, expressing either proline or leucine as the 463th amino acid. It was found that the variant with proline at this site was the more prevalent type of CTR among Japanese population.The allele frequencies of the calcitonin receptor (CTR) gene were compared between 46 breast cancer patients and 50 controls. The allele frequencies of CTR gene did not differ between them. There was no significant association of CTR allele frequencies histologicaly in invasive breast carcinomas. These results indicate that allelic variants of CTR gene is not significant risk factor to the development of breast carcinoma in Japanese.Further studies are needed to clear the function of CT or CTR in mammary tissue.