TCDD deregulates contact inhibition in rat liver oval cells via Ah receptor, JunD and cyclin A

WEISS, C, D FAUST, I SCHRECK, A RUFF, T FARWERCK, A MELENBERG, S SCHNEIDER, B OESCH-BARTLOMOWICZ, Jiřina PROCHÁZKOVÁ, Jan VONDRÁČEK, F OESCH a C DIETRICH. TCDD deregulates contact inhibition in rat liver oval cells via Ah receptor, JunD and cyclin A. Oncogene. USA: Nature Publishing Group, roč. 27, č. 15, s. 2198-2207. ISSN 0950-9232. doi:10.1038/sj.onc.1210859. 2008.

Základní údaje

• Originální název: TCDD deregulates contact inhibition in rat liver oval cells via Ah receptor, JunD and cyclin A
• Autoři: WEISS, C, D FAUST, I SCHRECK, A RUFF, T FARWERCK, A MELENBERG, S SCHNEIDER, B OESCH-BARTLOMOWICZ, Jiřina PROCHÁZKOVÁ, Jan VONDRÁČEK, F OESCH a C DIETRICH.
• Vydání: Oncogene, USA, Nature Publishing Group, 2008, 0950-9232.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Utajení: není předmětem státního či obchodního tajemství
• Impakt faktor: Impact factor: 7.216
• Doi: http://dx.doi.org/10.1038/sj.onc.1210859
• UT WoS: 000254621300010
• Klíčová slova anglicky: aryl hydrocarbon receptor; contact inhibition; cell cycle control; JunD; cyclin A; liver oval cells

Anotace

The aryl hydrocarbon receptor (AhR) is a transcription factor involved in physiological processes, but also mediates most, if not all, toxic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Activation of the AhR by TCDD leads to its dimerization with aryl hydrocarbon nuclear translocator (ARNT) and transcriptional activation of several phase I and II metabolizing enzymes. However, this classical signalling pathway so far failed to explain the pleiotropic hazardous effects of TCDD, such as developmental toxicity and tumour promotion. Thus, there is an urgent need to de. ne genetic programmes orchestrated by AhR to unravel its role in physiology and toxicology. Here we show that TCDD treatment of rat liver oval cells leads to induction of the transcription factor JunD, resulting in transcriptional upregulation of the proto-oncogene cyclin A which finally triggers a release from contact inhibition. Ectopic expression of cyclin A in confluent cultures overcomes G(1) arrest, indicating that increased cyclin A levels are indeed sufficient to bypass contact inhibition. Functional interference with AhR-, but not with ARNT, abolished TCDD-induced increase in JunD and cyclin A and prevented loss of contact inhibition. In summary, we have discovered a novel AhR- dependent and probably ARNT-independent signalling pathway involving JunD and cyclin A, which mediates TCDD-induced deregulation of cell cycle control.