The influence of matrix metalloproteinase-7 on early mammary tumorigenesis in the multiple intestinal neoplasia mouse.
The multiple intestinal neoplasia (Min/+) mouse, which carries a mutant adenomatous polyposis coli (Apc) allele, is a model for human familial colon cancer. Like the human syndrome caused by mutant APC, the Min/+ mouse syndrome shows susceptibility to tumors of other tissues, including the mammary gland. The matrix metalloproteinase (MMP) MMP-7 (matrilysin) gene is transcriptionally induced by signal transduction pathways resulting from loss of APC function, and contributes to the progression of benign and malignant intestinal epithelial cells. Mammary tumors that develop in Min/+ mice express MMP-7. To investigate whether mutant APC and MMP-7 can cooperate in mammary tumorigenesis, we compared N-ethyl-N-nitrosourea (ENU)-enhanced mammary tumor formation in Min/+ mice that were either wild-type or deficient in MMP-7. Min/+ mice lacking MMP-7 demonstrate a 60% reduction in the number of early focal lesions in the mammary gland at early, but not later, timepoints. We conclude that MMP-7 transiently influences early stage mammary tumorigenesis.
Hulboy
Diana L
DL
Department of Cancer Biology, Division of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Gautam
Shiva
S
Fingleton
Barbara
B
Matrisian
Lynn M
LM
D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor; D017931:DNA Primers; D005260:Female; D017353:Gene Deletion; D017491:Genes, APC; D005838:Genotype; D006801:Humans; D007414:Intestinal Neoplasms / Q000473:pathology*; D015674:Mammary Neoplasms, Animal / Q000201:enzymology* / Q000473:pathology; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009367:Neoplasm Staging
D014408:Biomarkers, Tumor; D017931:DNA Primers; D020783:Matrix Metalloproteinase 7