Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation
| Autor: | Nancy H. Colburn, Hidetoshi Yoshinaga, Shuning Zhan, Joan L. Cmarik, Sachiko Matsuhashi, Hongzhong Min, Glenn Hegamyer, Molly Kulesz-Martin |
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| Rok vydání: | 1999 |
| Předmět: |
Keratinocytes
Immunoblotting Gene Expression RNA-binding protein Biology Cell Line Mice Gene expression Sense (molecular biology) Tumor Cells Cultured Protein biosynthesis Animals Humans Neoplastic transformation RNA Messenger Mice Inbred BALB C Messenger RNA Multidisciplinary Proteins RNA-Binding Proteins Biological Sciences Molecular biology Transformation (genetics) Cell Transformation Neoplastic Phenotype Cell culture Protein Biosynthesis Tetradecanoylphorbol Acetate Rabbits Apoptosis Regulatory Proteins |
| Zdroj: | Proceedings of the National Academy of Sciences. 96:14037-14042 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | An mRNA differential display comparison of mouse JB6 promotion-sensitive (P+) and -resistant (P−) cells identified a novel gene product that inhibits neoplastic transformation. The JB6 P+ and P− cells are genetic variants that differ in their transformation response to tumor promoters; P+ cells form anchorage-independent colonies that are tumorigenic, and P− cells do not. A differentially displayed fragment,A7-1, was preferentially expressed in P− cells at levels ≥10-fold those in P+ cells, making its mRNA a candidate inhibitor of neoplastic transformation. AnA7-1cDNA was isolated that was identical to murinePdcd4gene cDNAs, also known asMA-3orTIS, and analogous to humanH731and197/15a. Until now, the function of the Pdcd4 protein has been unknown. Paralleling the mRNA levels, Pdcd4 protein levels were greater in P− than in P+ cells.Pdcd4mRNA was also expressed at greater levels in the less progressed keratinocytes of another mouse skin neoplastic progression series. To test the hypothesis that Pdcd4 inhibits tumor promoter-induced transformation, stable cell lines expressing antisensePdcd4were generated from parental P− cells. The reduction of Pdcd4 proteins in antisense lines was accompanied by acquisition of a transformation-sensitive (P+) phenotype. The antisense-transfected cells were reverted to their initial P− phenotype by overexpression of aPdcd4sense fragment. These observations demonstrate that the Pdcd4 protein inhibits neoplastic transformation. |
| Databáze: | OpenAIRE |
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