Ornithine Decarboxylase as a Target for Chemoprevention of Basal and Squamous Cell Carcinomas in Ptch1+/– Mice

March 2004 in “ Journal of Clinical Investigation ”

Xiuwei Tang, Arianna L. Kim, David J. Feith, Anthony E. Pegg, Justin Russo, Hong Zhang, Michelle Aszterbaum, Levy Kopelovich, Ervin H. Epstein, David R. Bickers, Mohammad Athar

The study demonstrated that ornithine decarboxylase (ODC) played a crucial role in the development of basal cell carcinomas (BCCs) in Ptch1+/– mice, which are predisposed to these tumors due to mutations in the PTCH gene. Overexpression of ODC in these mice accelerated BCC induction following UVB exposure, while inhibition of ODC through antizyme overexpression or oral administration of the ODC inhibitor α-difluoromethylornithine reduced BCC formation. These findings suggested that targeting ODC could be an effective chemopreventive strategy against BCCs in humans.

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Research cited in this study

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research A Definitive Role of Ornithine Decarboxylase in Photocarcinogenesis

67 citations, September 2001 in “American Journal Of Pathology”

Inhibiting ODC can prevent UV-induced skin cancer.

research Involvement of Follicular Stem Cells in Forming Not Only the Follicle but Also the Epidermis

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Hair follicle stem cells can form both hair follicles and skin.

research Co-Operation Between Follicular Ornithine Decarboxylase and v-Ha-ras Induces Spontaneous Papillomas and Malignant Conversion in Transgenic Skin

88 citations, August 1998 in “Carcinogenesis”

The study demonstrated that elevated levels of ornithine decarboxylase (ODC) and polyamines, when combined with a mutant Ha-ras gene, led to spontaneous tumor development in double transgenic mice. These mice, which were bred to carry both K6/ODC and v-Ha-ras transgenes, developed well-differentiated keratoacanthomas, some of which progressed to carcinomas within 2 months. The tumor development was dependent on ODC, as the use of the ODC inhibitor DFMO prevented tumor formation and caused regression. This indicated that ODC overexpression and activated Ha-ras were sufficient for malignant transformation, providing a model to study epithelial tumor development without chemical carcinogens or tumor promoters.

Related Research

2 / 2 results

research Ornithine Decarboxylase as a Target for Chemoprevention of Basal and Squamous Cell Carcinomas in Ptch1+/– Mice

64 citations, March 2004 in “Journal of Clinical Investigation”

The study demonstrated that ornithine decarboxylase (ODC) played a crucial role in the development of basal cell carcinomas (BCCs) in Ptch1+/– mice, which are predisposed to these tumors due to mutations in the patched (PTCH) gene. Overexpression of ODC in these mice accelerated BCC induction following UVB exposure, while inhibition of ODC through antizyme (AZ) overexpression or the use of the ODC inhibitor α-difluoromethylornithine reduced BCC formation. These findings suggested that targeting ODC could be an effective chemopreventive strategy for reducing BCCs in humans.

research Ornithine Decarboxylase as a Target for Chemoprevention of Basal and Squamous Cell Carcinomas in Ptch1+/– Mice

65 citations, March 2004 in “Journal of Clinical Investigation”