alexa Impact Of Hypoxia On The Pro Inflammatory Phenotype Of Human Prostate Cancer Cell Lines With Different Degree Of Differentiation
ISSN: 2157-7013

Journal of Cell Science & Therapy
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4th World Congress on Cell Science & Stem Cell Research
June 24-26, 2014 Valencia Conference Centre, Valencia, Spain

Ravenna Linda
Accepted Abstracts: J Cell Sci Ther
DOI: 10.4172/2157-7013.S1.030
Abstract
I n tumors, hypoxia induces a transcription program that promotes an aggressive phenotype. Recent studies have suggested that hypoxia is also a feature in prostate cancer and is associated with a poor prognosis. The hypoxia-inducible factors (HIF) α are the key transcription factors controlling the cellular response to hypoxia. Furthermore, prostate tumor progression is correlated with inflammation which is mainly regulated by NF-kB. A cross-talk between the NF-kB and the HIF pathways has been documented. The present study explored the hypoxic remodeling of the pro-inflammatory gene expression related to malignancy and the role of NF-kB in this process in well differentiated androgen dependent LNCaP and in less differentiated, androgen independent, highly metastatic DU145 and PC3 tumour prostate cells. Hypoxic treatments were carried in a sealed modular incubator chamber. NF-kB inhibition was obtained by parthenolide. Gene expression was evaluated by real time PCR and western blot. HIF1  was the main player in the response to hypoxia in all the examined cell lines while HIF2  did not appear modulated. A nuclear HIF3α protein was detectable only in DU145 and a late hypoxic induction was observed. Hypoxia activated the NF-kB pathway in DU145 and PC3 but not in LNCaP cells. DU145 and PC3 cells evidenced a higher normoxic expression and a more complete hypoxic induction of a representative subset of pro-inflammatory molecules with respect to LNCaP cells. NF-kB inhibitor parthenolide counteracted the hypoxia induced phenotype in DU145 and in PC3 but not in LNCaP cells. These results show that in androgen-dependent more differentiated tumor, the contribution of epithelial cell to the pro-inflammatory gene expression in both normoxia and hypoxia is low as compared to that of advanced cancer. Besides, NF-kB plays a crucial role in shifting the hypoxic DU145 and PC3 but not LNCaP cells towards a pro-inflammatory, more malignant phenotype. The author intend to silence HIF-1α to discriminate the specific role of HIF-1 α and NF-kB in this process. The knowledge of different involvement of these two pathways in different tumour phenotype could have useful fallout on clinical research and therapy
Biography
Ravenna Linda is a Researcher at the National Council of Research, Institute of Molecular Biology and Pathology, Roma, Italy. She graduated in Biological Sciences (1975), Researcher at Farmitalia Carlo Erba (1976-1981), Specialized in Microbiology (1987). She completed her PhD in Experimental Medicine (1995) and has published several papers in reputed journals. Her research interests are: a) Mutagenicity tests for new pharmaceutical molecules and mycotoxins. b) Effects of androgens and anti-androgens on proliferation, EGF, EGFR and AR expression in prostate cell lines. c) Estrogen regulation of EGFR transcription: molecular mechanisms and effects of selective estrogen receptors modulators (SERMs) d) Pro-inflammatory gene expression in prostate tumors. Role of hypoxic microenvironment on the activation of Hypoxia Inducible Factors, NF-kB and in the modulation of the pro inflammatory phenotype in prostate tumor cell lines
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