PTEN expression and methylation status in oral squamous cell carcinoma.
PTEN is a tumor suppressor gene located on chromosome10q23.3. In addition to genetic mutations and deletions, the down-regulation of PTEN has been found in various malignant tumors. However, little is known about the profile of PTEN gene in oral carcinomas. In this study, the expression profiles and genetic alterations of PTEN were examined in 113 oral squamous cell carcinoma (OSCC) cases and 9 OSCC-derived cell lines. An immunohistochemical analysis showed statistically significant differences in the immunohistochemical (IHC) scores for PTEN protein in normal tissues and in cancerous regions (P=0.0104), suggesting that PTEN protein expression is down-regulated in OSCC. No significant correlations existed between the down-regulation of PTEN protein expression and the clinicopathological features of the tumor. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed a lower PTEN mRNA expression in the 9 OSCC-derived cell lines examined, as compared to the normal oral epithelium cells. However, treatment with a demethylating reagent restored PTEN mRNA expression in 4 cell lines. No genetic mutations were detected in these cell lines by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. The results suggest that epigenetic changes may be related to the down-regulation of PTEN expression. We therefore conclude that PTEN is a crucial molecule in the tumorigenesis of OSCC.
Kurasawa
Yoshinori
Y
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Shiiba
Masashi
M
Nakamura
Megumi
M
Fushimi
Kazuaki
K
Ishigami
Takashi
T
Bukawa
Hiroki
H
Yokoe
Hidetaka
H
Uzawa
Katsuhiro
K
Tanzawa
Hideki
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human