title: Proliferation of cells and expression of RARs, RXRs and HPV viral E6 and E7 proteins in cervical cancer cell lines after treatment with ATRA.
abstract: All-trans retinoic acid (ATRA) is considered to be a potential chemotherapeutic drug due to its capability to regulate cell growth and differentiation. The effects of ATRA on the proliferation of cells and gene regulation are mediated by retinoid receptors (RAR and RXR), which belong to the nuclear receptor superfamily of ligand- inducible transcription factors. ATRA can act either as a growth inhibitor or growth promoter, according to the functional state of retinoic receptors. Thus, we have established the effect of ATRA on the proliferation of cervical cancer cells line HeLa and CaSki and expression of retinoids receptors as well as the viral HPV oncogenic proteins E6 and E7. ATRA had no effect on proliferation CaSki cells, but it stimulated the growth of HeLa cells, which depended on the incubation time and the concentration of ATRA in cell culture. The overexpression of RAR alpha in HeLa cells after the administration of 10(-7) mM ATRA was also observed 72 hours, and the decrease of CaSki by 60-90%. In the study of cervical cancer cell lines, the very low levels of other endogenous RAR and RXR receptors were observed. ATRA does not repress the expression of two viral oncoproteins E6 and E7 HPV16/18, which play a key role in carcinogenesis of the cervix. Our results support the suggestions that the cell response to vitamin A, and other retinoids in the diet, may depend on cell type, and that the cancer cells are differentially resistant to retinoids. Thus, despite the important biological functions of retinoids, the effects of retinoids in a supplementation in supra-physiological doses as well as their physiological action are difficult to define.
authors: Jan Dlugosz University in Czestochowa, Institute of Chemistry, Environmental Protection and Biotechnology, Częstochowa, Poland.
authors: Magdalena
authors: M
authors: Myga-Nowak
authors: Joanna
authors: J
authors: Pacholska-Bogalska
authors: Wojciech
authors: W
authors: Kwaśniewski
authors: Anna
authors: A
authors: Kwaśniewska
authors: Anna
authors: A
authors: Goździcka-Józefiak
mesh_terms: D015153:Blotting, Western; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D014212:Tretinoin