Calcitonin receptor polymorphism-function and diseases-

降钙素受体（CTRs）有三种亚型。第一种类型（类型1）在大鼠中含有465个氨基酸，在猪中含有468个氨基酸。第二种类型（2型）在第二胞外结构域中具有39个氨基酸的插入。第三种类型（类型3）在第一胞内结构域中具有16个氨基酸插入。从人卵巢癌细胞系中分离到的人CTR即属于这一类型。3.用与人CTR cDNA序列相对应的引物进行RT-PCR，分析了CTR转录本在7种人卵巢癌细胞系和手术标本中的表达。在所有样本中均检测到CTR mRNA。检测到比3型短48 bp的转录物，但未检测到2型和3型的转录物。以人基因组DNA为模板的PCR研究表明，该48 bp的序列构成外显子。这些结果表明1型和3型人类CTR是通过选择性剪接产生的，并且大多数人类CTR转录本是1型。对10个培养的人类肿瘤细胞系和117个人类血液样品的CTR的结构分析表明，在胞内结构域4的第1377个核苷酸处存在等位变异，表达脯氨酸或亮氨酸作为第463个氨基酸。结果发现，在日本人群中，降钙素受体（CTR）基因的等位基因频率以脯氨酸突变型最高，并对46例乳腺癌患者和50例对照者的CTR基因频率进行了比较。CTR基因的等位基因频率在两组间无差异。在浸润性乳腺癌中CTR等位基因频率与组织学无显著相关性。这些结果表明CTR基因的等位基因变异不是日本人乳腺癌发生的重要危险因素，CT或CTR在乳腺组织中的功能还需要进一步的研究。

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.