Matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression.
Matrix metalloproteinase 9 (MMP-9, also known as gelatinase B or 92-kd Type IV collagenase) is overexpressed in many human and murine cancers. We induced carcinomas in mice carrying a transgene that links the MMP-9 promoter to the reporter ss-galactosidase so that activation of the MMP-9 promoter wo...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2000
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| _version_ | 1797085711098183680 |
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| author | Kupferman, M Fini, M Muller, W Weber, R Cheng, Y Muschel, R |
| author_facet | Kupferman, M Fini, M Muller, W Weber, R Cheng, Y Muschel, R |
| author_sort | Kupferman, M |
| collection | OXFORD |
| description | Matrix metalloproteinase 9 (MMP-9, also known as gelatinase B or 92-kd Type IV collagenase) is overexpressed in many human and murine cancers. We induced carcinomas in mice carrying a transgene that links the MMP-9 promoter to the reporter ss-galactosidase so that activation of the MMP-9 promoter would be indicated by ss-galactosidase. Mammary carcinomas were induced by mating the MMP-9 promoter reporter transgenic mice with mice carrying a transgene for murine mammary tumor virus promoter linked to polyoma middle T antigen, a transgene that leads to rapid development of mammary tumors in female mice. None of the hyperplastic mammary glands and none of the carcinomas in situ expressed ss-galactosidase. However, all invasive tumors had evidence of ss-galactosidase expression. In addition to the breast carcinomas, a malignant teratoma in a female and a papillary adenocarcinoma in the pelvic region of a male arose and were also ss-galactosidase positive. We also induced skin tumors in the mice with the MMP-9 reporter transgene with 7, 12-dimethylbenz[a]anthracene (DMBA) treatment followed by phorbol 12 myristate 13-acetate (TPA). None of the papillomas or in situ carcinomas showed any ss-galactosidase expression, but expression was seen in invasive carcinoma. Although normal skin epithelial cells did not express ss-galactosidase, we did find staining in a few cells at the duct of the sebaceous gland at the base of the hair follicles. The MMP-9 reporter transgene did not lead to expression in the alveolar macrophages, confirming that additional upstream sequences are required for expression in macrophages. These experiments have revealed that MMP-9 promoter activity is induced coincident with invasion during tumor progression. Furthermore, this indicates that the more proximal upstream elements of the promoter are sufficient for MMP-9 transcription during tumor progression. |
| first_indexed | 2024-03-07T02:11:49Z |
| format | Journal article |
| id | oxford-uuid:a0ec3593-551f-4a3a-a658-8503a1fae65b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:11:49Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:a0ec3593-551f-4a3a-a658-8503a1fae65b2022-03-27T02:09:06ZMatrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a0ec3593-551f-4a3a-a658-8503a1fae65bEnglishSymplectic Elements at Oxford2000Kupferman, MFini, MMuller, WWeber, RCheng, YMuschel, RMatrix metalloproteinase 9 (MMP-9, also known as gelatinase B or 92-kd Type IV collagenase) is overexpressed in many human and murine cancers. We induced carcinomas in mice carrying a transgene that links the MMP-9 promoter to the reporter ss-galactosidase so that activation of the MMP-9 promoter would be indicated by ss-galactosidase. Mammary carcinomas were induced by mating the MMP-9 promoter reporter transgenic mice with mice carrying a transgene for murine mammary tumor virus promoter linked to polyoma middle T antigen, a transgene that leads to rapid development of mammary tumors in female mice. None of the hyperplastic mammary glands and none of the carcinomas in situ expressed ss-galactosidase. However, all invasive tumors had evidence of ss-galactosidase expression. In addition to the breast carcinomas, a malignant teratoma in a female and a papillary adenocarcinoma in the pelvic region of a male arose and were also ss-galactosidase positive. We also induced skin tumors in the mice with the MMP-9 reporter transgene with 7, 12-dimethylbenz[a]anthracene (DMBA) treatment followed by phorbol 12 myristate 13-acetate (TPA). None of the papillomas or in situ carcinomas showed any ss-galactosidase expression, but expression was seen in invasive carcinoma. Although normal skin epithelial cells did not express ss-galactosidase, we did find staining in a few cells at the duct of the sebaceous gland at the base of the hair follicles. The MMP-9 reporter transgene did not lead to expression in the alveolar macrophages, confirming that additional upstream sequences are required for expression in macrophages. These experiments have revealed that MMP-9 promoter activity is induced coincident with invasion during tumor progression. Furthermore, this indicates that the more proximal upstream elements of the promoter are sufficient for MMP-9 transcription during tumor progression. |
| spellingShingle | Kupferman, M Fini, M Muller, W Weber, R Cheng, Y Muschel, R Matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression. |
| title | Matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression. |
| title_full | Matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression. |
| title_fullStr | Matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression. |
| title_full_unstemmed | Matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression. |
| title_short | Matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression. |
| title_sort | matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression |
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