International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)

Table of Contents * Complex Genetics * Developmental Genetics * Gene Annotation * Gene Discovery * Genome Sequencing * Functional Genomics * Mutagenesis * Presentations * Verne Chapman Memorial Lecture

POSTER 4 - GENETICS OF 12-O-TETRADECANOYLPHORBOL-13-ACETATE (TPA) SKIN TUMOR PROMOTION

Dr Joe Angel
Univ. TX M.D Anderson Cancer Center
Science Park
1 Butcher Park Road
Smithville, Texas 78957 USA

Co-Author:  DiGiovanni J 
Institution:  University of Texas M.D Anderson Cancer Center

Tumor susceptibility genes modify the response of individuals to carcinogen exposure.  Multiple genes are involved and each gene contributes to, but is not solely responsible for pre-disposition to developing a particular type of cancer.  Dramatic differences in susceptibility to two-stage, initiation-promotion skin carcinogenesis have been detected in different mouse stocks and strains. Previous studies have shown that susceptibility to tumor promotion by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in genetic crosses of sensitive DBA/2 with relatively resistant C57BL/6 mice involves at least three genes.  One TPA promotion susceptibility locus, Psl1, has been mapped to distal chr 9.  This linkage has been confirmed in (C57BL/6 ´ BXD22)F₃ mice genetically selected to be homozygous for either C57BL/6 or DBA/2 alleles of distal chr 9 markers.  Additional TPA promotion susceptibility loci are being mapped in (C57BL/6 ´ BXD27)F₂ mice.  Like DBA/2 and BXD22, BXD27 mice are sensitive to TPA skin tumor promotion but inherited most of distal chr 9, including Psl1, from C57BL/6. Thus, TPA promotion sensitivity of the BXD27 strain is due to additional promotion susceptibility loci not linked to distal chr 9.  Preliminary analyses of the (C57BL/6 ´ BXD27)F₂ intercross mice for chromosomal regions previously weakly associated with TPA promotion susceptibility in genetic crosses of C57BL/6 and DBA/2 mice (chr 2, 4, 8, and 11) suggest a strong correlation of TPA promotion susceptibility with distal chr 2.  Further studies are underway to confirm this linkage.  Supported by NIEHS grant ES08355 and NIEHS Center grant ES0778.