Background and Objective Lung cancer is the leading cause of cancer death in both men and women in both China and worldwide. Apoptosis is a highly regulated,
BAG-1 is an anti-apoptotic protein that interacts with a variety of cellular molecules to inhibit apoptosis. It is also important in the prognosis of several human malignancies such as breast cancer. We have previousl...BAG-1 is an anti-apoptotic protein that interacts with a variety of cellular molecules to inhibit apoptosis. It is also important in the prognosis of several human malignancies such as breast cancer. We have previously cloned the human BAG-1 promoter. Using BAG-1 promoter as a probe, we identi ed a cDNA clone that encodes a novel BAG-1 promoter-binding protein, termed FLJ20420. The FLJ20420 protein speci cally bind to BAG-1 promoter (-353 to -128 bp) and decreased BAG-1 promoter activity ~30% by cotransfecting the pcDNA3.1-FLJ20420 and BGP-Luc BAG-1 promoter into lung cancer cell lines A549 and L9981. The FLJ20420 gene encodes a ~26kD protein localized in both cytoplasm and nucleus. Comparison of human FLJ20420 with mouse sequences showed a 90% homology with mouse gene, named CHCHD3. Furthermore, Northern blot revealed that FLJ20420 has low-level transcriptional expression in most human normal tissues (brain, placenta, lung, liver, kidney, pancreas and cervix) except in heart and skeletal muscle, and has a clear expression in most tumor cell lines. Knockdown of endogenous FLJ20420 significantly increased the expression of BAG-1 in A549 and L9981 cells, as analyzed by real-time PCR and western blotting. Gene array studies in lung cancer tissue samples indicated that there is a significant change in expression of FLJ20420 between the primary lung cancer and the paired normal lung tissues (P=0.0002), while BAG-1 has a significantly decreased expression in the primary lung cancers compared to the paired normal lung tissues (P=0.0001) , suggesting that the expression of BAG-1 was controlled by positive as well as negative transcription factors. Our observation was further confirmedby real-time PCR analysis of FLJ20420 and BAG-1 expressions in these tissues. Taken together, our results suggest that FLJ20420 functions as a down-regulator of BAG-1 and its expression may be involved in oncogenesis of human malignancy.展开更多
基金supported by the following grants to Qinghua ZHOU:The Key Project of National Natural Science Foundation of China (30430300)The Major Project of Tianjin Sci-Tech Support Programme (07SYSYS F05000)+3 种基金The Key Project of Tianjin Sci-Tech Support Programme (06YFS ZSF05300)The Building Project of Tianjin Sci-Tech Innovation Platform (07SYSYJC27900)863 National Major Projects (2006AA02A401)National Key Basic Research and Development Plan (973 Plan) program (20 07CBS914800)
文摘Background and Objective Lung cancer is the leading cause of cancer death in both men and women in both China and worldwide. Apoptosis is a highly regulated,
基金supported by grants from National Natural Science Foundation of China (Jun Chen, 30500221 Hongyu Liu, 30500496)
文摘BAG-1 is an anti-apoptotic protein that interacts with a variety of cellular molecules to inhibit apoptosis. It is also important in the prognosis of several human malignancies such as breast cancer. We have previously cloned the human BAG-1 promoter. Using BAG-1 promoter as a probe, we identi ed a cDNA clone that encodes a novel BAG-1 promoter-binding protein, termed FLJ20420. The FLJ20420 protein speci cally bind to BAG-1 promoter (-353 to -128 bp) and decreased BAG-1 promoter activity ~30% by cotransfecting the pcDNA3.1-FLJ20420 and BGP-Luc BAG-1 promoter into lung cancer cell lines A549 and L9981. The FLJ20420 gene encodes a ~26kD protein localized in both cytoplasm and nucleus. Comparison of human FLJ20420 with mouse sequences showed a 90% homology with mouse gene, named CHCHD3. Furthermore, Northern blot revealed that FLJ20420 has low-level transcriptional expression in most human normal tissues (brain, placenta, lung, liver, kidney, pancreas and cervix) except in heart and skeletal muscle, and has a clear expression in most tumor cell lines. Knockdown of endogenous FLJ20420 significantly increased the expression of BAG-1 in A549 and L9981 cells, as analyzed by real-time PCR and western blotting. Gene array studies in lung cancer tissue samples indicated that there is a significant change in expression of FLJ20420 between the primary lung cancer and the paired normal lung tissues (P=0.0002), while BAG-1 has a significantly decreased expression in the primary lung cancers compared to the paired normal lung tissues (P=0.0001) , suggesting that the expression of BAG-1 was controlled by positive as well as negative transcription factors. Our observation was further confirmedby real-time PCR analysis of FLJ20420 and BAG-1 expressions in these tissues. Taken together, our results suggest that FLJ20420 functions as a down-regulator of BAG-1 and its expression may be involved in oncogenesis of human malignancy.
