This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Noll, W. W. Articles by Brinckerhoff, C. E. Search for Related Content PubMed PubMed Citation Articles by Noll, W. W. Articles by Brinckerhoff, C. E.

(American Journal of Pathology. 2001;158:691-697.)
© 2001 American Society for Investigative Pathology

Regular Article

Loss of Heterozygosity on Chromosome 11q22-23 in Melanoma Is Associated with Retention of the Insertion Polymorphism in the Matrix Metalloproteinase-1 Promoter

Walter W. Noll^*, Dorothy R. Belloni^*, Joni L. Rutter, Craig A. Storm^*, Alan R. Schned^*, Linda Titus-Ernstoff, Marc S. Ernstoff^§ and Constance E. Brinckerhoff^§

From the Departments of Pathology,^*
Biochemistry,
Community and Family Medicine,
and Medicine,^§
Dartmouth Medical School, Hanover; and The Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire

Matrix metalloproteinase-1 (MMP-1, collagenase-1), which degrades interstitial collagen, is expressed at high levels by some tumor cells and is thought to enhance their invasiveness and metastatic potential. We recently described a common single nucleotide insertion polymorphism (2G allele) at -1,607 bp in the promoter of the MMP-1 gene that creates a binding site for the ETS family of transcription factors, and that is associated with enhanced transcription of this gene and increased enzyme activity. Allelic loss at the MMP-1 locus on chromosome 11 occurs in many tumors including melanoma, an invasive and aggressive cancer. We hypothesized that although loss of either the 1G or 2G allele from 1G/2G heterozygotes is random, retention of the transcriptionally more active 2G allele would favor tumor invasion and metastasis. As a result, a higher proportion of metastases would contain the 2G genotype than the 1G genotype. We report here the development of quantitative methods for assessing allelic loss at the MMP-1 locus, and demonstrate that 83% of the metastatic melanomas with loss of heterozygosity at this locus retained the 2G allele. This supports the hypothesis that retention of the 2G allele favors tumor invasion and metastasis in melanoma.

This article has been cited by other articles:

				B. A. Mercer, A. M. Wallace, C. E. Brinckerhoff, and J. M. D'Armiento Identification of a Cigarette Smoke-Responsive Region in the Distal MMP-1 Promoter Am. J. Respir. Cell Mol. Biol., January 1, 2009; 40(1): 4 - 12. [Abstract] [Full Text] [PDF]

				M. Sugimoto, S. Yoshida, S. Kennedy, M. Deguchi, N. Ohara, and T. Maruo Matrix Metalloproteinase-1 and -9 Promoter Polymorphisms and Endometrial Carcinoma Risk in a Japanese Population Reproductive Sciences, October 1, 2006; 13(7): 523 - 529. [Abstract] [PDF]

				K. K. Nelson, S. Subbaram, K. M. Connor, J. Dasgupta, X.-F. Ha, T.-C. Meng, N. K. Tonks, and J. A. Melendez Redox-dependent Matrix Metalloproteinase-1 Expression Is Regulated by JNK through Ets and AP-1 Promoter Motifs J. Biol. Chem., May 19, 2006; 281(20): 14100 - 14110. [Abstract] [Full Text] [PDF]

				R. Menon and S. J. Fortunato The Role of Matrix Degrading Enzymes and Apoptosis in Repture of Membranes Reproductive Sciences, October 1, 2004; 11(7): 427 - 437. [Abstract] [PDF]

				R. M. Wenham, B. Calingaert, S. Ali, K. McClean, R. Whitaker, R. Bentley, J. M. Lancaster, J. Schildkraut, J. Marks, and A. Berchuck Matrix Metalloproteinase-1 Gene Promoter Polymorphism and Risk of Ovarian Cancer Reproductive Sciences, September 1, 2003; 10(6): 381 - 387. [Abstract] [PDF]

				S. Harendza, D. H. Lovett, U. Panzer, Z. Lukacs, P. Kuhnl, and R. A. K. Stahl Linked Common Polymorphisms in the Gelatinase A Promoter Are Associated with Diminished Transcriptional Response to Estrogen and Genetic Fitness J. Biol. Chem., May 30, 2003; 278(23): 20490 - 20499. [Abstract] [Full Text] [PDF]

				K. K. Nelson, A. C. Ranganathan, J. Mansouri, A. M. Rodriguez, K. M. Providence, J. L. Rutter, K. Pumiglia, J. A. Bennett, and J. A. Melendez Elevated Sod2 Activity Augments Matrix Metalloproteinase Expression: Evidence for the Involvement of Endogenous Hydrogen Peroxide in Regulating Metastasis Clin. Cancer Res., January 1, 2003; 9(1): 424 - 432. [Abstract] [Full Text] [PDF]

				Y. Zhu, M. R. Spitz, L. Lei, G. B. Mills, and X. Wu A Single Nucleotide Polymorphism in the Matrix Metalloproteinase-1 Promoter Enhances Lung Cancer Susceptibility Cancer Res., November 1, 2001; 61(21): 7825 - 7829. [Abstract] [Full Text] [PDF]

				B. Zhang, S. Dhillon, I. Geary, W. M. Howell, F. Iannotti, I. N.M. Day, and S. Ye Polymorphisms in Matrix Metalloproteinase-1, -3, -9, and -12 Genes in Relation to Subarachnoid Hemorrhage Stroke, September 1, 2001; 32(9): 2198 - 2202. [Abstract] [Full Text] [PDF]