Expression of epidermal ornithine decarboxylase and nuclear proto-oncogenes in phorbol ester tumor promotion-sensitive and -resistant mice.
This study was undertaken to assess the effects of a single or two sequential topical applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the expression of c-fos, c-jun, junB, c-myc, and ornithine decarboxylase (ODC) in promotion-sensitive SSIN mice and the relatively promotion-resistant C57BL/6 strain. Northern blot analysis demonstrated that a single promoting dose of TPA induced ODC mRNA expression 10- to 15-fold in both strains. Treatment of each strain with a second dose of TPA, 48 h (in C57BL/6 mice) or 72 h (in SSIN mice) after the first, led to hyperinduction of ODC activity. Although this involved transcription of new ODC mRNA, the hyperinduction of ODC enzyme activity was primarily posttranscriptional. Induction of c-fos mRNA or protein was maximal about 3 h after a single treatment in either strain but was sustained for at least 6 h in C57BL/6 mice. In contrast, two treatments of SSIN mice with TPA caused a rapid, strong c-fos induction 1-2 h after treatment, whereas C57BL/6 mice responded no more strongly than after a single treatment. c-jun mRNA and protein were induced only slightly in either strain, but junB was induced about fivefold in SSIN mice and tenfold in C57BL/6 mice. Although c-myc was induced to comparable levels in both strains, the response was more prolonged in C57BL/6 mice. Compared with SSIN mice, C57BL/6 mice responded to TPA treatment, in general, with changes in proto-oncogene mRNA to a higher level or for longer or both. Thus, although small differences in the expression of these genes were observed, they were not positively correlated with the differential sensitivity of SSIN and C57BL/6 mice toward tumor promotion by phorbol esters, with the possible exception of c-fos.
Kennard
M D
MD
University of Texas M. D. Anderson Cancer Center, Smithville 78957.
Kang
D C
DC
Montgomery
R L
RL
Butler
A P
AP
D000818:Animals; D003043:Cocarcinogenesis; D004351:Drug Resistance; D004817:Epidermis / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008810:Mice, Inbred C57BL; D018632:Mice, Inbred SENCAR; D009687:Nuclear Proteins / Q000096:biosynthesis*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D013045:Species Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate