Expression patterns and polymorphisms of PTCH in Chinese hepatocellular carcinoma patients.
Aberrant activation of Hedgehog signaling pathway leads to pathological consequences in a variety of human tumors. PTCH (PTCH1), the receptor of Hedgehog pathway, is reported to function as a gatekeeper in tumor formation. Here we report, by semi-quantitative RT-PCR, PTCH expression was found in 38 hepatocellular carcinoma (HCC) patients (66%). Evidences from real time quantitative RT-PCR further indicate that compared to their matched nontumorous liver tissue, PTCH exhibit a higher expression in well and moderate differentiated tumor, but a lower expression in poorly differentiated tumor. Immunohistochemical staining showed PTCH protein was detected in the cytoplasm of 56.3% HCC samples (9/16). For the first time, we investigate the polymorphisms of PTCH in HCC. First we sequenced the recognized mutation hot spots regions of PTCH of 38 HCC samples. Two previously reported single nucleotide polymorphisms (SNPs) and a novel SNP A1056G were identified. Then we examined these three SNPs in 171 HCC samples and 162 normal liver samples. However, statistic analysis showed none of these SNPs was statistically significant for association with HCC. In conclusion, our data suggest that PTCH is involved in early stage tumor development and the Hh pathway in Chinese HCC is activated by ligand expression but not by mutation.
Fu
Xinhui
X
Department of Hepatobiliary Surgery, The First Affiliate Hospital, Sun Yat-Sen (Zhongshan) University, Guangzhou 510089, Guangdong, People's Republic of China.
Wang
Qian
Q
Chen
Xilin
X
Huang
Xiaohui
X
Cao
Liangqi
L
Tan
Haoxiang
H
Li
Wen
W
Zhang
Longjuan
L
Bi
Jiong
J
Su
Qiao
Q
Chen
Lianzhou
L
D000328:Adult; D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002681:China; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface