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c-Jun/AP-1 pathway-mediated cyclin D1 expression participates in low dose arsenite-induced transformation in mouse

Dongyun Zhang1, Jingxia Li, Jimin Gao

  • 1Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.

Toxicology and Applied Pharmacology
|December 9, 2008
PubMed

Insights

Low dose arsenite exposure triggers skin cell transformation by activating the c-Jun/AP-1 pathway. This process involves cyclin D1, a key molecule in arsenite-induced carcinogenesis.

Area of Science:

  • Environmental Toxicology
  • Molecular Carcinogenesis
  • Dermatology

Background:

  • Arsenic is a known human carcinogen linked to skin cancer.
  • Previous research indicated arsenite induces cell transformation via ERK, not JNK pathways.

Purpose of the Study:

  • To investigate downstream pathways in low-dose arsenite-induced cell transformation.
  • To identify key molecular events in arsenite-mediated skin carcinogenesis.

Main Methods:

  • Utilized mouse epidermal JB6 Cl41 cells.
  • Assessed activation of c-Jun/AP-1 pathway.
  • Employed dominant-negative c-Jun (TAM67) and cyclin D1 siRNA.

Main Results:

  • Low-dose arsenite activated the c-Jun/AP-1 pathway.
  • TAM67 expression blocked arsenite-induced transformation.
  • Cyclin D1 inhibition impaired arsenite-induced anchorage-independent growth.

Conclusions:

  • c-Jun/AP-1 pathway activation is crucial for arsenite-induced cell transformation.
  • Cyclin D1 is a key downstream mediator in this process.
  • These findings elucidate mechanisms of skin carcinogenesis by low-dose arsenic.

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