title: Abnormal structure and expression of PTEN/MMAC1 gene in human uterine cancers.
abstract: The PTEN/MMAC1 gene, located on human chromosome 10q23, has recently been implicated as a candidate tumor suppressor gene in human cancers. In the present study, 12 uterine cancer cell lines and 87 uterine cancers of various grades and histological type were analyzed for PTEN/MMAC1 gene. Three of 44 endometrial carcinoma (7%) showed no PTEN/MMAC1 mRNA expression by RT-PCR analysis. Sequencing analysis of entire coding region of PTEN/MMAC1 gene revealed mutations in three of six endometrial cancer cell lines (50%) and 17 of 44 endometrial cancer tissues (39%). In contrast, for cervical cancers, only one of six cancer cell lines (2%) showed mutation, and one of 43 cancer tissues (2%) had an abnormality. Overall, 36% of the abnormal spots were located in exon 5, 24% were in exon 8, 16% were in exon 3, and 8% were in exon 6, and single cases of abnormality were found in exons 1, 4, and 7. Our results revealed that, in total, 60% of abnormalities were clustered in exons 5 and 8. Exon 5 is a functional domain of the PEN/MMAC1 gene, and therefore, abnormalities in this region may be important for loss of PTEN/MMAC1 gene function. Finally, we found a high frequency of PTEN/MMAC1 gene abnormalities in endometrial carcinomas but a low frequency in cervical carcinomas. These findings suggest that disruption of PTEN/MMAC1 by mutation or absence of expression may contribute to the pathogenesis or neoplastic evolution in a large proportion of endometrial carcinomas but in a small proportion of cervical carcinomas.
authors.affiliation: Department of Obstetrics & Gynecoloy, Asahikawa Medical College, Asahikawa, Japan. yaginum@asahikawa-med.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Yaginuma
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Ishiya
authors.forename: A
authors.initials: A
authors.lastname: Morizaki
authors.forename: Y
authors.initials: Y
authors.lastname: Katoh
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
mesh_terms: D018076:DNA, Complementary / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics; D005260:Female; D052138:Genes, Neoplasm; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D002583:Uterine Cervical Neoplasms / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human