Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diploid mouse embryos containing only maternal DNA (parthenotes) fail, in part, because the inner cell mass does not induce the trophoblast to grow. In this study, we asked whether any of the defects in parthenotes may arise from alterations in trophoblast function. We examined the expression of genes important for normal trophoblast function and found several trophoblast genes that were expressed at normal levels in the primary trophoblast cells of parthenotes: E-cadherin, a cell adhesion molecule, was expressed normally in both the ICM and trophectoderm of parthenogenetic blastocysts and blastocyst outgrowths; the gene for Hxt, a basic helix-loop-helix factor that regulates trophoblast development, was expressed in both zygotic and parthenogenetic giant cells; placental lactogen-1, a hormone that is normally secreted by trophoblast giant cells, was expressed in most of both parthenogenetic and normal trophoblast cells; and the 92 kDa matrix metalloproteinase, gelatinase B, also known as MMP-9, was secreted at equivalent levels by both zygotic and parthenogenetic blastocyst outgrowths. However, once the outgrowths had developed, a subpopulation of trophoblast cells in parthenogenetic embryos had decreased DNA replication and significantly fewer nucleoli per nucleus than did zygotic embryos. Moreover, the parthenogenetic trophoblast cells growing out from blastocysts had a decreased viability in culture. These data suggest that, although parthenogenetic embryos are able to initiate primary trophoblast differentiation, the stability and continued differentiation of trophoblast giant cells may be abnormal. Our data support the hypothesis that the deficiency of secondary trophoblast giant cells may contribute to the decline of parthenogenetic embryos and suggest that the factors controlling this subset of trophoblast are distinct from those for primary trophoblast.
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PMID:Functional analysis of trophoblast giant cells in parthenogenetic mouse embryos. 909 6

Id proteins are inhibitors of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We have shown that ectopic expression of Id-1 in murine mammary epithelial cells resulted in loss of differentiation and gain of invasive and proliferative abilities. Moreover, Id-1 was highly expressed in aggressive breast cancer cells in culture and in biopsies from infiltrating carcinomas. In contrast to Id-1, we found that, in vitro and in vivo, Id-2 mRNA and protein were up-regulated as mammary epithelial cells lost proliferative capacity and initiated differentiation. We further determined that this up-regulation of Id-2 was a necessary step toward a fully differentiated phenotype in breast cells. Here we show that one of the components of the extracellular matrix network, laminin, is responsible for the increase in Id-2 expression during differentiation. We also show that Id-2 expression is inversely correlated with the rate of proliferation in murine mammary epithelial cells and that Id-2 is expressed at a higher level in differentiated human breast cancer cells in comparison with very aggressive and metastatic cells. When reintroduced in aggressive breast cancer cells, Id-2 is able to reduce their proliferative and invasive phenotypes and decrease their level of matrix metalloproteinase 9 secretion as well as increase syndecan-1 expression. Moreover, little Id-2 protein expression is detectable in human biopsies from aggressive and invasive carcinomas in comparison with in situ carcinomas. In conclusion, Id-2 expression not only follows a pattern opposite to that of Id-1 during mammary gland development and breast cancer progression but also appears to act as an important protein for the maintenance of a differentiated and noninvasive phenotype in normal and transformed breast cells.
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PMID:Role of Id-2 in the maintenance of a differentiated and noninvasive phenotype in breast cancer cells. 1461 2

Inhibitors of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We previously determined that ID1 was highly expressed in aggressive salivary gland cancer (SGC) cells in culture. Here, we show that ID2 is also expressed in aggressive SGC cells. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. Moreover, ID2 knockdown almost completely suppresses invasion and the expression of matrix metalloproteinase 9. In conclusion, ID2 expression maintains an aggressive phenotype in SGC cells, and ID2 repression triggers a reduction in cell aggressiveness. ID2 therefore represents a potential therapeutic target during SGC progression. ID proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. ID2 therefore represents a potential therapeutic target during SGC progression.
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PMID:Targeting ID2 expression triggers a more differentiated phenotype and reduces aggressiveness in human salivary gland cancer cells. 2761 Jun 6