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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
|
pubmed:dateCreated |
1994-6-27
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pubmed:abstractText |
We describe the selection of 3 new multidrug-resistant cell lines derived from tumor cells of different metastatic phenotypes within the Dunning R3327 model of rat prostatic carcinoma. Cell lines of weak (AT2) and strong (AT3 and MAT-LyLu) metastatic behavior were cultured in vitro and challenged with doxorubicin at progressively increasing concentrations. Chemosensitivity was determined colorimetrically by release of precipitated formazan pigment (MTT assay). Expression of the multidrug-resistance glycoprotein (P-170) was monitored immunocytochemically and by Western blotting using monoclonal antibody C219. The behavior of the parental and resultant drug-resistant cells was assessed by their growth in syngeneic rats. Doxorubicin challenge of the initially drug-sensitive parental prostatic carcinoma cell lines resulted in the rapid development of multidrug resistance together with simultaneous expression of P-glycoprotein. While lung and lymph-node metastases developed in host animals inoculated with parental AT3 and MAT-LyLu cells, no metastases developed in the multidrug-resistant progeny of these cell lines. This study has shown that Dunning rat prostate-carcinoma cell lines, previously sensitive to different cytotoxic agents, rapidly become multidrug-resistant and express P-glycoprotein following exposure to doxorubicin. Furthermore, development of multidrug resistance is associated with a less aggressive tumor phenotype and loss of metastatic potential. Nevertheless, it is unlikely that the non-metastatic phenotype of Dunning rat prostatic carcinoma cells is solely associated with expression of P-glycoprotein. These new multidrug-resistant cell lines exhibiting an altered behavioral phenotype will provide a valuable model with which to analyze the relationship between expression of P-glycoprotein and the metastatic phenotype of prostatic carcinoma cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Jun
|
pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
1
|
pubmed:volume |
57
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
719-26
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pubmed:dateRevised |
2007-7-24
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pubmed:meshHeading |
pubmed-meshheading:7910810-Animals,
pubmed-meshheading:7910810-Carcinoma,
pubmed-meshheading:7910810-Carrier Proteins,
pubmed-meshheading:7910810-Doxorubicin,
pubmed-meshheading:7910810-Drug Resistance,
pubmed-meshheading:7910810-Male,
pubmed-meshheading:7910810-Membrane Glycoproteins,
pubmed-meshheading:7910810-Neoplasm Metastasis,
pubmed-meshheading:7910810-P-Glycoprotein,
pubmed-meshheading:7910810-Prostatic Neoplasms,
pubmed-meshheading:7910810-Rats,
pubmed-meshheading:7910810-Tumor Cells, Cultured
|
pubmed:year |
1994
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pubmed:articleTitle |
Establishment and in vivo characterization of multidrug-resistant dunning R3327 rat prostate-carcinoma cell-lines.
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pubmed:affiliation |
Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
|