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

J 2008

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 et al.

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

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 7.216

DOI

https://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

Změněno: 30. 10. 2017 14:34, Mgr. Jiřina Procházková, Ph.D.

Anotace

V originále

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.

Citovat

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, 2008, roč. 27, č. 15, s. 2198-2207. ISSN 0950-9232. Dostupné z: https://doi.org/10.1038/sj.onc.1210859.

@article{1394034,
   author = {Weiss, C and Faust, D and Schreck, I and Ruff, A and Farwerck, T and Melenberg, A and Schneider, S and OeschandBartlomowicz, B and Procházková, Jiřina and Vondráček, Jan and Oesch, F and Dietrich, C},
   article_location = {USA},
   article_number = {15},
   doi = {https://doi.org/10.1038/sj.onc.1210859},
   keywords = {aryl hydrocarbon receptor; contact inhibition; cell cycle control; JunD; cyclin A; liver oval cells},
   language = {eng},
   issn = {0950-9232},
   journal = {Oncogene},
   title = {TCDD deregulates contact inhibition in rat liver oval cells via Ah receptor, JunD and cyclin A},
   volume = {27},
   year = {2008}
}

TY  - JOUR
ID  - 1394034
AU  - Weiss, C - Faust, D - Schreck, I - Ruff, A - Farwerck, T - Melenberg, A - Schneider, S - Oesch-Bartlomowicz, B - Procházková, Jiřina - Vondráček, Jan - Oesch, F - Dietrich, C
PY  - 2008
TI  - TCDD deregulates contact inhibition in rat liver oval cells via Ah receptor, JunD and cyclin A
JF  - Oncogene
VL  - 27
IS  - 15
SP  - 2198-2207
EP  - 2198-2207
PB  - Nature Publishing Group
SN  - 09509232
KW  - aryl hydrocarbon receptor
KW  - contact inhibition
KW  - cell cycle control
KW  - JunD
KW  - cyclin A
KW  - liver oval cells
N2  - 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.
ER  -

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. \textit{Oncogene}. USA: Nature Publishing Group, 2008, roč.~27, č.~15, s.~2198-2207. ISSN~0950-9232. Dostupné z: https://doi.org/10.1038/sj.onc.1210859.

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