Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma.
PinX1 was isolated as a Pin2/TRF1 binding protein that also binds to the telomerase catalytic subunit hTERT. The gene is a potent telomerase inhibitor and a putative tumor suppressor since it inhibits telomerase activity and affects tumorigenicity in nude mice. This study investigated aberrations of PinX1 gene in gastrointestinal tract carcinomas (GITCs). We examined mutations, mRNA expression and promoter methylation of PinX1 gene in 15 GITC cell lines, and 20 patients with primary GITC. We found a missense mutation at codon 254 (AGC/TGC) in a colon and an esophageal carcinoma cell line, and in cancerous and matching normal tissues of 2 patients with primary GITC (10%). It might be a benign polymorphism. No hyper-methylation was found in the promoter region and the treatment by 5-Aza-2'-deoxycytidine did not affect PinX1 mRNA expression level in any of the cell lines. It was concluded that the human PinX1 does not affect tumorigenesis of human GITC.
Akiyama
Yuji
Y
Department of Pathology, Iwate Medical University, School of Medicine, Morioka 020-8505, Japan. chihaya@iwate-med.ac.jp
Maesawa
Chihaya
C
Wada
Kei
K
Fujisawa
Kentaro
K
Itabashi
Tetsuya
T
Noda
Yoshinori
Y
Honda
Takehisa
T
Sato
Nobuhiro
N
Ishida
Kaoru
K
Takagane
Akinori
A
Saito
Kazuyoshi
K
Masuda
Tomoyuki
T
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017422:Sequence Analysis, DNA; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; C440808:PINX1 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D019098:Telomerase; D001374:Azacitidine