title: Initiation of premature senescence by Bcl-2 in hypoxic condition.
abstract: Senescence, a state of cell cycle arrest, has been regarded as an intrinsic barrier to malignance. Although being repressed in most immortal tumors, the genetic program of senescence can be reactivated by critical regulators, including the apoptosis regulator Bcl-2. We showed here that hypoxic condition resulted in an irreversible senescence-like phenotype with increased expression of Bcl-2 in mouse melanoma B16 cells. In CoCl2-simulating hypoxic condition, characteristic morphological alterations and increased activity of senescence-associated β-galactosidase (SA-β-gal) can be detected with high level of Bcl-2, which was confirmed by western blot and co-staining of SA-β-gal and Bcl-2 by immunocytochemistry. Accordingly, Bcl-2 silence by specific siRNA ahead of hypoxia treatment interrupted the senescent development. Moreover Bcl-2 overexpression led to early onset of senescence. We propose that Bcl-2 is required to initiate and maintain the senescent phenotype. In addition, p53 and p16 were not involved in hypoxia-induced senescence according to the expression levels during senescent process. These results suggest that when encountering harmful stress (hypoxia), melanoma cells overexpress Bcl-2 and turn to senescence, a permanent cell-cycle arrest, for prolonged survival.
authors: Department of Neurosurgery, The Second Hospital of Tianjin Medical University Tianjin, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Neurosurgery, The Second Hospital of Tianjin Medical University Tianjin, China.
authors: Desheng
authors: D
authors: Wang
authors: Department of Neurosurgery, The Second Hospital of Tianjin Medical University Tianjin, China.
authors: Hong
authors: H
authors: Li
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse; D003035:Cobalt; D001616:beta-Galactosidase; C018021:cobaltous chloride
keywords: Bcl-2; Senescence; hypoxia; melanoma