| First Author | Wheeler DL | Year | 2003 |
| Journal | Cancer Res | Volume | 63 |
| Issue | 12 | Pages | 3037-42 |
| PubMed ID | 12810623 | Mgi Jnum | J:83969 |
| Mgi Id | MGI:2664459 | Citation | Wheeler DL, et al. (2003) Inhibition of the Development of Metastatic Squamous Cell Carcinoma in Protein Kinase C epsilon Transgenic Mice by alpha-Difluoromethylornithine Accompanied by Marked Hair Follicle Degeneration and Hair Loss. Cancer Res 63(12):3037-42 |
| abstractText | The role of 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated polyamine biosynthesis in the development of metastatic squamous cell carcinoma (mSCC) in protein kinase C epsilon (PKCepsilon) transgenic mice was determined. TPA treatment induced epidermal ornithine decarboxylase (ODC) activity and putrescine levels approximately 3-4-fold more in PKCepsilon transgenic mice than their wild-type littermates. Development of mSCC by the 7,12-dimethylbenz(a)anthracene (100 nmol)-TPA (5 nmol) protocol in PKCepsilon transgenic mice was completely prevented by administration of the suicide inhibitor of ODC alpha-difluoromethylornithine (DFMO, 0.5% w/v) in the drinking water during TPA promotion. However, DFMO treatment led to marked hair loss in PKCepsilon transgenic mice. DFMO treatment-associated hair loss in PKCepsilon transgenic mice was accompanied by a decrease in the number of intact hair follicles. These results indicate that TPA-induced ODC activity and the resultant accumulation of putrescine in PKCepsilon transgenic mice are linked to growth and maintenance of hair follicles, and the development of mSCC. Severe hair loss observed in PKCepsilon transgenic mice on DFMO during skin tumor promotion has not been reported before in the prevention of cancer in other animal models or in human cancer prevention trials. |
