Počet záznamů: 1
Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes
- 1.
SYSNO ASEP 0546654 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes Tvůrce(i) Krkoška, Martin (BFU-R) ORCID
Svobodová, Jana (BFU-R) ORCID
Kabátková, Markéta (BFU-R) ORCID
Zapletal, Ondřej (BFU-R) ORCID
Vaculová, Alena (BFU-R) RID, ORCID
Nekvindová, J. (CZ)
Vondráček, Jan (BFU-R) RID, ORCIDCelkový počet autorů 7 Číslo článku 152897 Zdroj.dok. Toxicology. - : Elsevier - ISSN 0300-483X
Roč. 461, SEP 2021 (2021)Poč.str. 10 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. IE - Irsko Klíč. slova aryl-hydrocarbon receptor ; factor-kappa-b ; beta-catenin ; human cyp1a1 ; p300 ; expression Vědní obor RIV FR - Farmakologie a lékárnická chemie Obor OECD Pharmacology and pharmacy CEP NV17-28231A GA MZd - Ministerstvo zdravotnictví Způsob publikování Omezený přístup Institucionální podpora BFU-R - RVO:68081707 UT WOS 000696272700006 EID SCOPUS 85113778859 DOI https://doi.org/10.1016/j.tox.2021.152897 Anotace Cytochrome P450 family 1 (CYP1) enzymes contribute both to metabolism of xenobiotics and to the control of endogenous levels of ligands of the aryl hydrocarbon receptor (AhR). Their activities, similar to other CYPs, can be altered in tumor tissues. Here, we examined a possible role of proliferative/survival pathways signaling, which is often deregulated in tumor cells, and possible links with p300 histone acetyltransferase (a transcriptional co-activator) in the control of CYP1 expression, focusing particularly on CYP1A1. Using cell models derived from human liver, we observed that the induction of CYP1A1 expression, as well as other CYP1 enzymes, was reduced in exponentially growing cells, as compared with their non-dividing counterparts. The siRNAmediated inhibition of proliferation/pro-survival signaling pathway effectors (such as beta-catenin and/or Hippo pathway effectors YAP/TAZ) increased the AhR ligand-induced CYP1A1 mRNA levels in liver HepaRG cells, and/ or in colon carcinoma HCT-116 cells. The activation of proliferative Wnt/beta-catenin signaling in HCT-116 cells reduced both the induction of CYP1 enzymes and the binding of p300 to the promoter of CYP1A1 or CYP1B1 genes. These results seem to indicate that aberrant proliferative signaling in tumor cells could suppress induction of CYP1A1 (or other CYP1 enzymes) via competition for p300 binding. This mechanism could be involved in modulation of the metabolism of both endogenous and exogenous substrates of CYP1A1 (and other CYP1 enzymes), with possible further consequences for alterations of the AhR signaling in tumor cells, or additional functional roles of CYP1 enzymes. Pracoviště Biofyzikální ústav Kontakt Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Rok sběru 2022 Elektronická adresa https://www.sciencedirect.com/science/article/pii/S0300483X21002201?via%3Dihub
Počet záznamů: 1