Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Invasive growth requires degradation of extracellular matrix. Altered expression of matrix degrading enzymes may indicate an increased potential for invasive growth. We determined the expression patterns of matrix-metalloproteinases (MMP)-1, -2, and -3 and of the tissue inhibitors of metalloproteinases (TIMP)-1 and -2 by in situ hybridization with isotopically labeled RNA probes in normal breast tissue (n=6), fibrocystic disease (n=20), five cases of which contained radial scars, lobular carcinoma in situ (CLIS; n=5), ductal carcinoma in situ (DCIS; n=9) and invasive carcinomas (n=24). Only a few cells displayed MMP-1- and MMP-2-specific labeling in normal breast tissue and fibrocystic disease. Noninvasive ductal carcinomas showed elevated MMP-2 transcript levels in peritumor stromal cells in the absence of significant MMP-1 specific signals. In general, compared with adjacent normal breast tissue, a gradual increase of MMP-2 was found in noninvasive to invasive cancers. Invasive ductal and lobular carcinomas displayed co-expression of MMP-1 and MMP-2 by stromal cells, mainly of the invasion front, with high signal intensity particularly in high-grade invasive carcinomas. Tumor cells and peritumor stroma showed low MMP-3 transcript levels, especially in medullary carcinomas. TIMP-1 and -2 transcript levels were increased in invasive carcinomas correlating with the histological grade. These RNA expression patterns suggest an increased invasive potential in breast carcinomas even prior to histologically overt invasive growth.
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PMID:Matrix-metalloproteinases 1, 2, and 3 and their tissue inhibitors 1 and 2 in benign and malignant breast lesions: an in situ hybridization study. 1062 98

Several members of the ETS family of transcription factors contribute to tumorigenesis in many different tissues, including breast epithelium. The ESX gene is an epithelial-specific Ets member that is particularly relevant to breast cancer. ESX is amplified in early breast cancers, it is overexpressed in human breast ductal carcinoma in situ, and there may be a positive feedback loop between the HER2/neu proto-oncogene and ESX. Despite this progress in our understanding of ESX, its ability to regulate tumor-related gene expression and to modulate breast cell survival, remain unknown. Here we show that HA-ESX stimulates the collagenase and HER2/neu promoters, but fails to activate an intact stromelysin promoter. However, HA-ESX activates, in a dose-dependent manner, a heterologous promoter containing eight copies of the Ets binding site derived from the stromelysin gene (p8Xpal-CAT). Analysis of the ability of constructs encoding nine Ets family members to activate the HER2/neu promoter revealed three patterns of gene activation: (1) no effect or repressed promoter activity (Elk-1 and NET); (2) intermediate activity (ER81, GABP, ESX, and HA-Ets-2); and, (3) maximal activity (Ets-1, VP-16-Ets-1, and EHF). Based on these observations, we also determined whether ESX is capable of conferring a survival phenotype upon immortalized, but nontransformed and ESX negative MCF-12A human breast cells. Using a colony formation assay, we found that HA-ESX and HA-Ets-2, mediated MCF-12A cell survival rates that approached those generated by oncogenic V12 Ras, whereas empty vector resulted in negligible colony formation. By contrast, in immortalized and transformed T47D breast cancer cells, which express both HER2/neu and ESX, we found that antisense and dominant-negative HA-ESX inhibited T47D colony formation, whereas control vector allowed formation of many colonies. These results are significant because they show that HA-ESX is able to differentially activate several malignancy-associated gene promoters, and that ESX expression is required for cellular survival of nontransformed MCF-12A and transformed T47D human mammary cells.
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PMID:The epithelial-specific ETS transcription factor ESX/ESE-1/Elf-3 modulates breast cancer-associated gene expression. 1271 34

Breast cancer is the second leading cause of cancer death for women in the United States. In 2005, about 215,000 cases of invasive breast cancer (IBC) and 50,000 cases of ductal carcinoma in situ will be diagnosed and 40,000 women will die of IBC in the US. Yet there is presently no molecular marker that can be used to detect a precancerous state or identify which premalignant lesions will develop into invasive breast cancer. Here we report the gene expression analysis of atypical ductal hyperplastic tissues from patients with and without a history of breast cancer. We identify MMP-1 as a candidate marker that may be useful for identification of breast lesions that can develop into cancer.
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PMID:Identification of MMP-1 as a putative breast cancer predictive marker by global gene expression analysis. 1586 12