Loss of tyrosinase activity confers increased skin tumor susceptibility in mice

Anna Saran, Monica Spinola, Simonetta Pazzaglia, Bernard Peissel, Cecilia Tiveron, Laura Tatangelo, Mariateresa Mancuso, Vincenzo Covelli, Lisa Giovannelli, Vanessa Pitozzi, Carmen Pignatiello, Silvano Milani, Piero Dolara, Tommaso A. Dragani

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Abstract

The tyrosinase (Tyr) gene encodes the enzyme tyrosinase that catalyses the conversion of L-tyrosine into DOPA (3,4-dihydroxypheaylalanine)-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 TyrCys 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 TyrCys 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.
Original languageEnglish
Pages (from-to)4130 - 4135
Number of pages6
JournalOncogene
Volume23
Issue number23
DOIs
Publication statusPublished - 20 May 2004
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Saran, A., Spinola, M., Pazzaglia, S., Peissel, B., Tiveron, C., Tatangelo, L., ... Dragani, T. A. (2004). Loss of tyrosinase activity confers increased skin tumor susceptibility in mice. Oncogene, 23(23), 4130 - 4135. https://doi.org/10.1038/sj.onc.1207565