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Bax gene disruption alters the epidermal response to ultraviolet irradiation and in vivo induced skin carcinogenesis

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Bcl-2 family member proteins are differentially expressed in skin and in non-melanoma skin cancer (NMSC). To elucidate the contribution of bcl-2 and bax proteins to epidermal differentiation and skin carcinogenesis, we investigated keratinocyte proliferation, differentiation and tumourigenesis in bcl-2-/- and bax-/- mice. The rate and pattern of proliferation and spontaneous cell death in the bcl-2-/- and bax-/- mice were not different from control mice. The epidermis of bcl-2-/- and bax-/- expressed sightly higher levels of cytokeratin 1 and loricrin compared to control littermates. The apoptotic response to ultraviolet-induced genotoxic stress was assessed by quantitating TUNEL positive cells. Bax-/- keratinocytes showed a significant resistance to UV-induced cell death compared to control mice. The life-span of bcl-2-/- mice precluded an assessment of bcl-2 gene disruption on in vivo tumourigenesis. A significant increase in tumour incidence was observed in bax-/- mice compared to control mice in two-step chemical carcinogenesis studies. These findings suggest that bcl-2 and bax gene products may be important determinants of normal keratinocyte differentiation and response to genotoxic stress in vivo, and indicate that bax may provide a tumour suppressor effect during skin carcinogenesis.
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Document Type: Research Article

Affiliations: Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA

Publication date: March 1, 2001

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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