Correlation between expression of the matrix metalloproteinase-1 gene in ovarian cancers and an insertion/deletion polymorphism in its promoter region.
Matrix metalloproteinases (MMPs), a family of closely related enzymes that degrade the extracellular matrix, are likely to be involved in invasion and metastasis of tumor cells. A guanine (G) insertion/deletion polymorphism within the promoter region of MMP-1 influences the transcription of this gene; i.e., the 2G (insertion-type) promoter possesses greater transcriptional activity than the 1G (deletion-type) promoter. To investigate whether this feature contributes to cancer development and/or progression, we genotyped 163 ovarian cancer patients for the polymorphism and then analyzed levels of expression of the MMP-1 gene in their tumors. The proportion of patients who were either heterozygotes or homozygotes for the 2G allele was significantly higher than that observed among 150 individuals without cancer (P = 0.028). Moreover, the levels of MMP-1 expression in cancer tissues among the patients carrying 2G alleles were elevated significantly in comparison with 1G homozygotes (P = 0.0038). By stimulating degradation of extracellular matrix, an excess of MMP-1 production may enhance development and/or rapid progression of ovarian cancers.
Kanamori
Y
Y
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Japan.
Matsushima
M
M
Minaguchi
T
T
Kobayashi
K
K
Sagae
S
S
Kudo
R
R
Terakawa
N
N
Nakamura
Y
Y
D017364:Collagenases / Q000235:genetics*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D020781:Matrix Metalloproteinase 1; D010051:Ovarian Neoplasms / Q000201:enzymology*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D017364:Collagenases; D020781:Matrix Metalloproteinase 1