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: Y Yaginuma, T Yamashita, T Ishiya, A Morizaki, Y Katoh, T Takahashi, H Hayashi, M Ishikawa
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 27 Issue 2 Pg. 110-6 (Feb 2000) ISSN: 0899-1987 [Print] United States
• PMID: 10657903 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Wiley-Liss, Inc.

Chemical References

• DNA, Complementary
• Tumor Suppressor Proteins
• Phosphoric Monoester Hydrolases
• PTEN Phosphohydrolase
• PTEN protein, human

Topics

• DNA, Complementary (genetics)
• Endometrial Neoplasms (genetics)
• Female
• Genes, Neoplasm
• Genes, Tumor Suppressor
• HeLa Cells
• Humans
• PTEN Phosphohydrolase
• Phosphoric Monoester Hydrolases (genetics)
• Polymorphism, Single-Stranded Conformational
• Reverse Transcriptase Polymerase Chain Reaction
• Sequence Analysis, DNA
• Tumor Cells, Cultured
• Tumor Suppressor Proteins
• Uterine Cervical Neoplasms (genetics)