DNA mismatch repair gene MLH1 induces apoptosis in prostate cancer cells
| Autor: | Yozo Mitsui, Soichiro Yamamura, Rajvir Dahiya, Ankurpreet Gill, Darryn K. Wong, Guoren Deng, Shahana Majid, Yuichiro Tanaka, Inik Chang, Norio Nonomura, Takeshi Chiyomaru, Hiroshi Hirata, Hiroaki Shiina, Shinichiro Fukuhara, Sharanjot Saini |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Small interfering RNA congenital hereditary and neonatal diseases and abnormalities Mice Nude Apoptosis Biology urologic and male genital diseases Transfection DNA Mismatch Repair c-Abl Piperazines Mice DU145 Cell Line Tumor Gene expression Animals Humans Phosphorylation Proto-Oncogene Proteins c-abl neoplasms Protein Kinase Inhibitors Adaptor Proteins Signal Transducing Cell growth MLH1 apoptosis prostate cancer nutritional and metabolic diseases Nuclear Proteins Prostatic Neoplasms digestive system diseases Imatinib mesylate Pyrimidines Oncology Cell culture Benzamides Cancer research Imatinib Mesylate Heterografts MutL Protein Homolog 1 Research Paper |
| Zdroj: | Oncotarget |
| Popis: | Mismatch repair (MMR) enzymes have been shown to be deficient in prostate cancer (PCa). MMR can influence the regulation of tumor development in various cancers but their role on PCa has not been investigated. The aim of the present study was to determine the functional effects of the mutL-homolog 1 (MLH1) gene on growth of PCa cells. The DU145 cell line has been established as MLH1-deficient and thus, this cell line was utilized to determine effects of MLH1 by gene expression. Lack of MLH1 protein expression was confirmed by Western blotting in DU145 cells whereas levels were high in normal PWR-1E and RWPE-1 prostatic cells. MLH1-expressing stable transfectant DU145 cells were then created to characterize the effects this MMR gene has on various growth properties. Expression of MLH1 resulted in decreased cell proliferation, migration and invasion properties. Lack of cell growth in vivo also indicated a tumor suppressive effect by MLH1. Interestingly, MLH1 caused an increase in apoptosis along with phosphorylated c-Abl, and treatment with MLH1 siRNAs countered this effect. Furthermore, inhibition of c-Abl with STI571 also abrogated the effect on apoptosis caused by MLH1. These results demonstrate MLH1 protects against PCa development by inducing c-Abl-mediated apoptosis. |
| Databáze: | OpenAIRE |
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