Zaphiropoulos P G, Undén A B, Rahnama F, Hollingsworth R E, Toftgård R
Department of Bioscience, Center for Nutrition and Toxicology, Karolinska Institute, Huddinge, Sweden.
Cancer Res. 1999 Feb 15;59(4):787-92.
By a combination of cDNA library screening, rapid amplification of cDNA ends analysis, and BAC sequencing, a novel human patched-like gene (PTCH2) has been cloned and sequenced. The genomic organization is similar to PTCH1 with 22 exons and, by radiation hybrid mapping, PTCH2 has been localized to chromosome 1p33-34, a region often lost in a variety of tumors. Several alternatively spliced mRNA forms of PTCH2 were identified, including transcripts lacking segments thought to be involved in sonic hedgehog binding and mRNAs with differentially defined 3' terminal exons. In situ hybridization revealed high expression of PTCH2 transcripts in both familial and sporadic basal cell carcinomas in similarity to what has been observed for PTCH1, suggesting a negative regulation of PTCH2 by PTCH1. This finding tightly links PTCH2 with the sonic hedgehog/PTCH signaling pathway, implying that PTCH2 has related, but yet distinct, functions than PTCH1.
通过cDNA文库筛选、cDNA末端快速扩增分析和BAC测序相结合的方法，一个新的人类类patched基因（PTCH2）被克隆并测序。其基因组结构与PTCH1相似，有22个外显子，通过辐射杂种定位，PTCH2被定位到1p33 - 34染色体区域，该区域在多种肿瘤中常发生缺失。已鉴定出PTCH2的几种可变剪接mRNA形式，包括缺少被认为参与音猬因子结合的片段的转录本以及具有不同定义的3'末端外显子的mRNA。原位杂交显示，与PTCH1的情况类似，PTCH2转录本在家族性和散发性基底细胞癌中均有高表达，提示PTCH1对PTCH2有负调控作用。这一发现将PTCH2与音猬因子/PTCH信号通路紧密联系起来，意味着PTCH2具有与PTCH1相关但又不同的功能。
