Abstract
Recent studies demonstrated that a single guanine insertion polymorphism in a matrix metalloprotease‐1 promoter created an Ets binding site and affected the elevation of the transcriptional level of matrix metalloproteinase‐1 (MMP‐1). Furthermore, in tumor cell lines derived from melanoma and breast cancer, the incidence of the 2G/2G genotype was significantly higher than that in the normal population. To evaluate the contribution of this polymorphism in endometrial carcinomas, we genotyped 100 endometrial carcinomas and then analyzed immunoexpression of MMP‐1 in these carcinomas. We found that endometrial carcinoma patients showed a significantly higher rate of 1G/2G or 2G/2G genotype than control individuals, and that tumors containing the 2G allele(a) expressed MMP‐1 protein more frequently than those with 1G/1G genotype. Therefore, the single nucleotide polymorphism at the MMP‐1 promoter affected the expression level of the MMP‐1 protein, which may result in the association with more aggressive character in endometrial carcinoma. Our result suggests that the presence of 2G polymorphism at the MMP‐1 promoter may be one of the risk factors for the development and/or progression of endometrial carcinoma.
Keywords: Matrix metalloproteinase‐1, Single nucleotide polymorphism, Human endometrial carcinoma
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REFERENCES
- 1. ) American Cancer Society . “Cancer Facts & Figures‐1995” ( 1995. ). American Cancer Society; , Atlanta . [Google Scholar]
- 2. ) Abeler , V. M. and Kjorstad , K. E.Endometrial adenocarcinoma in Norway. A study of a total population . Cancer , 67 , 3093 – 3103 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Hart , I. R. and Saini , A.Biology of tumor metastasis . Lancet , 339 , 1453 – 1457 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Kohn , E. C. and Liotta , L. A.Molecular insights into cancer invasion: strategies for prevention and intervention . Cancer Res. , 55 , 1856 – 1862 ( 1995. ). [PubMed] [Google Scholar]
- 5. ) Borden , P. and Heller , R.Transcriptional control of matrix metalloproteases and the tissue inhibitors of matrix metalloproteinase . Crit. Rev. Eukaryot. Gene Expr. , 7 , 159 – 178 ( 1997. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Stetler‐Stevenson , W. G. , Liotta , L. A. and Kleiner , D. E.Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis . FASEB J. , 7 , 1434 – 1441 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Murray , G. I. , Duncan , M. E. , Oneil , P. , Melvin , W. T. and Forthergill , J. E.Matrix metalloproteinase‐1 is associated with poor prognosis in colorectal cancer . Nat. Med. , 2 , 461 – 462 ( 1996. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Murray , G. I. , Duncan , M. E. , Oneil , P. , Mckay , J. A. , Melvin , W. T. and Forthergill , J. E.Matrix metalloproteinase‐1 is associated with poor prognosis in oesophageal cancer . J. Pathol. , 185 , 256 – 261 ( 1998. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Rutter , J. L. , Mitchell , T. I. , Buttice , G. , Meyers , J. , Gusella , J. F. , Ozelius , L. J. and Brinckerhoff , C. E.A single nucleotide polymorphism in the matrix metalloproteinase‐1 promoter creates an Ets binding site and augments transcription . Cancer Res. , 58 , 5321 – 5325 ( 1998. ). [PubMed] [Google Scholar]
- 10. ) Kanamori , Y. , Matsushima , M. , Minaguchi , T. , Kobayashi , K. , Sagae , S. , Kudo , R. , Terakawa , N. and Nakamura , Y.Correlation between expression of the matrix metalloproteinase‐1 gene in ovarian cancers and an insertion/deletion polymorphism in its promoter region . Cancer Res. , 59 , 4225 – 4227 ( 1999. ). [PubMed] [Google Scholar]
- 11. ) Sato , T. , Tanigami , A. , Yamakawa , K. , Akiyama , F. , Kasumi , F. , Sakamoto , G. and Nakamura , Y.Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer . Cancer Res. , 50 , 7184 – 7189 ( 1990. ). [PubMed] [Google Scholar]
- 12. ) Scully , R. E. , Bonfiglo , T. A. , Kurman , R. J. , Silverberg , S. G. and Wilkinson , E. J.Histological typing of female genital tract tumors . In“International Histological Classification of Tumors ,” 2nd Ed. , World Health Organization ( 1996. ). Springer‐Verlag; , Berlin . [Google Scholar]
- 13. ) FIGO Stages— Revision . Gynecol. Oncol .