Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have reported that transin RNA, a 1.9-kb RNA coding for a novel, secreted proteinase, was overexpressed during the progression of benign mouse skin papillomas to malignant squamous cell carcinomas (SCCs) induced by a two-stage protocol (Proc Natl Acad Sci USA 83:9413, 1986). Recently a high degree of similarity has been demonstrated between rabbit stromelysin, a secreted metalloproteinase that degrades proteoglycans found in the basement membrane and the amino acid sequence predicted in rat transin cDNA. DNA sequencing of a mouse cDNA isolated from an SCC (initiated by 7,12-dimethylbenz[a]anthracene [DMBA] and promoted by 12-O-tetradecanoylphorbol-13-acetate [TPA]) showed greater than 85% nucleotide similarity and 90% amino acid similarity to the rat transin-1 cDNA nucleotide and predicted amino acid sequences. Using this mouse transin cDNA clone as a probe (labeled with 32P) we found enhanced levels of transin mRNA transcripts in SCCs induced by a protocol giving rise to metastatic tumors (repeated N-methyl-N-nitroso-N'-nitroguanidine [MNNG] treatments) compared with the level found in SCCs induced by a protocol that had a lower probability of giving rise to metastatic tumors (MNNG initiation followed by TPA promotion). A study of primary SCCs and metastatic lesions induced by repeated benzo[a]pyrene treatment showed that the levels of transin mRNA transcripts were reduced in the metastatic lesions in comparison to the primary tumors. Southern analysis of the DNA isolated from epidermis, papillomas, and SCCs indicated that neither transin gene amplification nor rearrangement accounted for increased levels of the transin mRNA transcripts. These data suggest a role for enhanced levels of transin production in the invasion and metastasis of chemically induced SCCs.
 ...
PMID:Expression pattern of a gene for a secreted metalloproteinase during late stages of tumor progression. 315 Dec 58

Chick embryo has been used as a model system for evaluating the metastatic potential of tumor cells. We have previously demonstrated that expression of the tissue inhibitor of matrix metalloproteinase-I (TIMP-I) gene can suppress liver colonization of tumor cels in chick embryo, probably by inhibiting the activity of matrix metalloproteinases (MMP) produced by tumor cells. In an attempt to identify MMP associated with liver colonization, we examined 24 human tumor cell lines for their potential to form metastatic colonies in chick-embryo liver after the cells had been inoculated into the chorioallantoic membrane (CAM) vein. We compared the results with the mRNA expression of MMP (MMP-I, MMP-2, MMP-3, MMP-9) studied previously. Three of 8 cell lines from mesenchymal tumors (fibrosarcoma HT1080, osteosarcomas SK-ES and MNNG/HOS) and 2 of 16 cell lines from epithelial tumors (gastric carcinoma KKLS and bladder carcinoma T24) proliferated in the livers. MMP-2 and MMP-9 were the enzymes whose transcripts were more frequently expressed in these 5 metastatic cell lines (MMP-1; 2/5, MMP-2; 4/5, MMP-3; 0/5, MMP-9; 3/5), but other cell lines that did not form liver colonies expressed the transcripts at lower frequency (MMP-2; 7/19, MMP-9; 3/19). Although either or both MMP-2 and MMP-9 transcripts were expressed in 4 of the 5 metastatic cell lines, they were undetectable in T24 cells. However, induced expression of both enzymes was detected by immunostaining in the T24 cells colonized in the liver. Thus, type-IV collagenases expressed by tumor cells may play a role in facilitating colonization in chick embryos.
 ...
PMID:Expression of type-IV collagenases in human tumor cell lines that can form liver colonies in chick embryos. 826 76