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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
1987-9-23
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pubmed:abstractText |
Mutant human beta-actin genes were introduced into normal human (KD) fibroblasts and the derivative cell line HuT-12, which is immortalized but nontumorigenic, to test their ability to promote conversion to the tumorigenic state. Transfected substrains of HuT-12 fibroblasts that expressed abundant levels of mutant beta-actin (Gly-244----Asp-244) produced subcutaneous tumors in athymic mice after long latent periods (1.5 to 3 months). However, transfected substrains of KD fibroblasts retained their normal finite life span in culture and consequently were incapable of producing tumors. Substrains of HuT-12 cells transfected with the wild-type beta-actin gene and some transfected strains that expressed low or undetectable levels of mutant beta-actin did not produce tumors. Cell lines derived from transfectant cell tumors always exhibited elevated synthesis of the mutant beta-actin, ranging from 145 to 476% of the level expressed by the transfected cells that were inoculated to form the tumor. In general, primary transfectant cells that expressed the highest levels of mutant beta-actin were more tumorigenic than strains that expressed lower levels. The tumor-derived strains were stable in tumorigenicity and produced tumors with shortened latent periods of only 2 to 4 weeks. These findings imply that the primary transfectant strains develop subpopulations of cells that are selected to form tumors because of their elevated rate of exogenous mutant beta-actin synthesis. Actin synthesis and accumulation of gamma-actin mRNA from the endogenous beta- and gamma-actin genes were diminished in tumor-derived strains, apparently to compensate for elevated mutant beta-actin synthesis and maintain the normal cellular concentration of actin. Synthesis of the transformation-sensitive tropomyosin isoforms was decreased along with mutant beta-actin expression. Such modulations in tropomyosin synthesis are characteristically seen in transformation of avian, rodent, and human fibroblasts. Our results suggest that this mutant beta-actin contributes to the neoplastic phenotype of immortalized human fibroblasts by imposing a cytoarchitectural defect and inducing abnormal expression of cytoskeletal tropomyosins.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-165499,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-2869410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-2996000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-3460482,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-3614198,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-3785208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-3837182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-3859366,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-4000123,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-4033781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-4053036,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-4055761,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-418410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6092933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6095033,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6201399,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6272310,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6290897,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6293052,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6304115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6315714,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6318314,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6332316,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6352074,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6646124,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6722823,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6892569,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6893954,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-6966280,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-7067038,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3614199-7199389
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0270-7306
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2467-76
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:3614199-Actins,
pubmed-meshheading:3614199-Animals,
pubmed-meshheading:3614199-Cell Line,
pubmed-meshheading:3614199-Cell Transformation, Neoplastic,
pubmed-meshheading:3614199-Gene Expression Regulation,
pubmed-meshheading:3614199-Homeostasis,
pubmed-meshheading:3614199-Humans,
pubmed-meshheading:3614199-Mice,
pubmed-meshheading:3614199-Mice, Nude,
pubmed-meshheading:3614199-Mutation,
pubmed-meshheading:3614199-Neoplasms, Experimental,
pubmed-meshheading:3614199-Oncogenes,
pubmed-meshheading:3614199-Phenotype,
pubmed-meshheading:3614199-Transfection,
pubmed-meshheading:3614199-Tropomyosin
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pubmed:year |
1987
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pubmed:articleTitle |
Expression of transfected mutant beta-actin genes: transitions toward the stable tumorigenic state.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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