| First Author | Saran A | Year | 2004 |
| Journal | Oncogene | Volume | 23 |
| Issue | 23 | Pages | 4130-5 |
| PubMed ID | 15007389 | Mgi Jnum | J:90844 |
| Mgi Id | MGI:3044861 | Doi | 10.1038/sj.onc.1207565 |
| Citation | Saran A, et al. (2004) Loss of tyrosinase activity confers increased skin tumor susceptibility in mice. Oncogene 23(23):4130-5 |
| abstractText | The tyrosinase (Tyr) gene encodes the enzyme tyrosinase that catalyses the conversion of L-tyrosine into DOPA (3,4-dihydroxyphenylalanine)-quinone. The albino mutation abrogates functional activity of tyrosinase resulting in deficiency of melanin pigment production in skin and retina. Tyr maps to a region in the central position of Chromosome 7 that contains a skin tumor-modifier locus. We rescued the albino mutation in transgenic mice to assess a possible role of Tyr gene in two-stage skin carcinogenesis. Transgenic expression of the functional Tyr(Cys) allele in albino mice (Tyr(Ser)) caused a reduction in skin papilloma multiplicity, in four independent experiments and at three dose levels of DMBA (9,10-dimethyl-1,2-benzanthracene). In vitro mechanistic studies demonstrated that transfection of the Tyr(Cys) allele in a human squamous cell carcinoma cell line (NCI-H520) increases tyrosinase enzyme activity and confers resistance to hydrogen peroxide-induced oxidative DNA damage. These results provide direct evidence that the Tyr gene can act as a skin cancer-modifier gene, whose mechanism of action may involve modulation of oxidative DNA damage. |
