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10.18632/oncotarget.8301

http://scihub22266oqcxt.onion/10.18632/oncotarget.8301
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C5029701!5029701 !27015368
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suck abstract from ncbi


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pmid27015368
      Oncotarget 2016 ; 7 (17 ): 24284-302
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  • The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor cell invasiveness and neuroendocrine differentiation in prostate cancer cells #MMPMID27015368
  • Labrecque MP ; Takhar MK ; Nason R ; Santacruz S ; Tam KJ ; Massah S ; Haegert A ; Bell RH ; Altamirano-Dimas M ; Collins CC ; Lee FJ ; Prefontaine GG ; Cox ME ; Beischlag TV
  • Oncotarget 2016[Apr]; 7 (17 ): 24284-302 PMID27015368 show ga
  • Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1? and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1. In this report, we further characterized the role Rb plays in mediating hypoxia-regulated genetic programs by stably ablating Rb expression with retrovirally-introduced short hairpin RNA in LNCaP and 22Rv1 human prostate cancer cells. DNA microarray analysis revealed that loss of Rb in conjunction with hypoxia leads to aberrant expression of hypoxia-regulated genetic programs that increase cell invasion and promote neuroendocrine differentiation. For the first time, we have established a direct link between hypoxic tumor environments, Rb inactivation and progression to late stage metastatic neuroendocrine prostate cancer. Understanding the molecular pathways responsible for progression of benign prostate tumors to metastasized and lethal forms will aid in the development of more effective prostate cancer therapies.
  • |*Cell Differentiation [MESH]
  • |Apoptosis [MESH]
  • |Biomarkers, Tumor/*genetics [MESH]
  • |Cell Movement [MESH]
  • |Cell Proliferation [MESH]
  • |Gene Expression Profiling [MESH]
  • |Gene Regulatory Networks [MESH]
  • |Humans [MESH]
  • |Hypoxia/*genetics [MESH]
  • |Male [MESH]
  • |Neoplasm Invasiveness [MESH]
  • |Neuroendocrine Cells/metabolism/*pathology [MESH]
  • |Prostatic Neoplasms/*genetics/metabolism/*pathology [MESH]
  • |Retinoblastoma Protein/genetics/*metabolism [MESH]


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