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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1992-11-23
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pubmed:abstractText |
Invasion of basement membranes by cancer cells is a critical step in metastasis, which requires the coordinated expression of specific genes such as laminin receptors and metalloproteinases. Estradiol and progesterone modulate the clinical progression of steroid-sensitive breast cancers; however, little is known about the molecular regulation of the invasive phenotype by these hormones. We therefore examined the effects of 10 nM estradiol and/or 10 nM progestin R5020 on the expression of 2 non-integrin laminin binding proteins, the 67-kDa laminin receptor (67LR) and HLBP31 as well as the 72-kDa type-IV collagenase (MMP-2) and its inhibitor, TIMP-2, in steroid-receptor-positive (T47D and MCF-7) and -negative (MDA-MB 231) human breast-cancer cells. The relative steady-state level of 67LR mRNA was increased 2- to 3-fold by estradiol in both MCF-7 (p < 0.001) and T47D (p < 0.001) cells, also by R5020, alone or in combination with estradiol, in T47D cells (p < 0.001) and to a much less extent in MCF-7 cells. HLBP31 mRNA and protein levels were increased 2- to 3-fold (p < 0.001) by R5020 alone or in combination with estradiol, but not by estradiol alone. None of the steroid treatments affected the expression or activity of MMP-2. Interestingly, however, TIMP-2 mRNA levels and protein expression in MCF-7 and T47D cells were 50% down-regulated (p < 0.001) by treatment with R5020 or R5020 plus estradiol, but not by treatment with estradiol alone. None of these genes were modulated in steroid-independent MDA-MB231 cells. The data suggest that estradiol and progesterone might act as coordinators regulating specific genes in the steroid-sensitive breast-cancer cell, leading to the acquisition of the metastatic phenotype.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Collagenases,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Promegestone,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Laminin,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Inhibitor of...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
653-7
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pubmed:dateRevised |
2007-7-24
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pubmed:meshHeading |
pubmed-meshheading:1399148-Breast Neoplasms,
pubmed-meshheading:1399148-Collagenases,
pubmed-meshheading:1399148-Estradiol,
pubmed-meshheading:1399148-Female,
pubmed-meshheading:1399148-Gene Expression Regulation,
pubmed-meshheading:1399148-Humans,
pubmed-meshheading:1399148-Matrix Metalloproteinase 9,
pubmed-meshheading:1399148-Neoplasm Invasiveness,
pubmed-meshheading:1399148-Neoplasm Metastasis,
pubmed-meshheading:1399148-Neoplasm Proteins,
pubmed-meshheading:1399148-Promegestone,
pubmed-meshheading:1399148-RNA, Messenger,
pubmed-meshheading:1399148-Receptors, Laminin,
pubmed-meshheading:1399148-Tissue Inhibitor of Metalloproteinase-2,
pubmed-meshheading:1399148-Tumor Cells, Cultured
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pubmed:year |
1992
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pubmed:articleTitle |
Genes involved in tumor invasion and metastasis are differentially modulated by estradiol and progestin in human breast-cancer cells.
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pubmed:affiliation |
Tumor Invasion and Metastasis Section, National Cancer Institute, Bethesda, MD 20892.
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pubmed:publicationType |
Journal Article
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