This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Angel, J. M. Articles by DiGiovanni, J. Search for Related Content PubMed PubMed Citation Articles by Angel, J. M. Articles by DiGiovanni, J.

Identification of Novel Genetic Loci Contributing to 12-O-Tetradecanoylphorbol-13-acetate Skin Tumor Promotion Susceptibility in DBA/2 and C57BL/6 Mice¹

The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957

Genetic differences in susceptibility to two-stage skin carcinogenesis have been known for many years. Studies of genetic crosses of sensitive DBA/2 with resistant C57BL/6 mice suggested that multiple autosomal genes determine the sensitivity of these mice to 12-O-tetradecanoylphorbol-13-acetate (TPA) skin tumor promotion. Previous studies mapped one promotion susceptibility locus, Psl1, to distal chromosome 9. Analysis of TPA promotion susceptibility in (C57BL/6 x DBA/2)F₁ x C57BL/6 mice and B x D recombinant inbred mouse strains suggested tentative associations of promotion susceptibility with several other chromosomal regions. To confirm these associations (C57BL/6 x BxD27)F₂ mice analyzed for TPA promotion susceptibility were genotyped for polymorphic genetic markers mapping to chromosomal regions for which tentative associations had been previously detected. BxD27 mice are sensitive to TPA skin tumor promotion but carry the C57BL/6 allele of Psl1. Because Psl1 does not segregate in this cross, its effect on TPA promotion susceptibility is the same for all mice in the cross. The results of this analysis support the mapping of three novel promotion susceptibility loci to chromosomes 1, 2, and 19. Psl2 maps near D2Mit229 on distal chromosome 2, and inheritance of the dominant DBA/2 allele results in increased sensitivity to TPA. Psl3 maps near D1Mit511 on distal chromosome 1. Interestingly, inheritance of an allele from the resistant C57BL/6 parent results in increased sensitivity to TPA. Psl3 appears to have an additive affect, with heterozygous mice having a stronger response to TPA than mice homozygous for the DBA/2 allele and a weaker response to TPA than mice homozygous for the C57BL/6 allele. Psl4 maps near D19Mit38 on distal chromosome 19 and inheritance of the dominant C57BL/6 allele results in decreased TPA sensitivity. Analysis of the combined effects of these loci on TPA promotion susceptibility indicates that they contribute independently to the overall sensitivity to TPA.

This article has been cited by other articles:

				C. T. Luke, C. E. Oki-Idouchi, J. M. Cline, and P. S. Lorenzo RasGRP1 Overexpression in the Epidermis of Transgenic Mice Contributes to Tumor Progression during Multistage Skin Carcinogenesis Cancer Res., November 1, 2007; 67(21): 10190 - 10197. [Abstract] [Full Text] [PDF]

				M. Wood, T. Udagawa, Y. Hida, and R. J. D'Amato X-Linked Dominant Growth Suppression of Transplanted Tumors in C57BL/6J-scid Mice Cancer Res., July 1, 2005; 65(13): 5690 - 5695. [Abstract] [Full Text] [PDF]