Mitogen-regulated protein/proliferin mRNA induction following single applications of tumor promoters to murine skin

• Published in: Molecular carcinogenesis 2005-07, Vol.43 (3), p.117-129
• Main Author: Parfett, Craig L.J.
• Format: Article
• Language: English
• Subjects: Acetone; Animals; benzoyl peroxide; Benzoyl Peroxide - toxicity; Blotting, Northern; Carcinogens - toxicity; CAS 16561-29-8; CAS 94-36-0; Cell Line; gene expression; Gene Expression Profiling - methods; Glycoproteins - genetics; Intercellular Signaling Peptides and Proteins; Kinetics; Mice; Mice, Inbred C3H; Promoter Regions, Genetic; RNA, Messenger - genetics; Skin - drug effects; Skin - pathology; tetradecanoylphorbol acetate; Tetradecanoylphorbol Acetate - toxicity; Transcription, Genetic - drug effects
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.20110

Mitogen‐regulated protein/proliferin (mrp/plf) gene family transcripts rise in abundance as a response to diverse chemical and physical agents that promote morphological transformation in the murine C3H/10T1/2 cultured cell model of multi‐step carcinogenesis. To determine if proliferin genes respond to tumor promoters in vivo, RNA was extracted from the whole skin of SENCAR mice after single applications of 2 or 20 μg 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA); 3.2 or 32 nmole), 20 or 40 mg benzoyl peroxide (BPO; 83, 165 μmole), or acetone vehicle alone (2.72 mmole). RNA samples were prepared from treated skin areas, 2–48 h after painting. Mrp/plf‐mRNA was not detected in Northern blot hybridizations, but large increases in mRNAs for ornithine decarboxylase gene and mRNA (odc), v‐jun oncogene‐related transcription factor gene and mRNA (junB), egr1 (early growth response protein gene and mRNA) were measured relative to beta 2 microglobulin gene and mRNA (b2m) mRNA in response to TPA. BPO induced small relative changes in these mRNAs. Reverse transcriptase (RT)‐polymerase chain reactions (PCR) detected fully‐processed MRP/plf‐mRNA 16–48 h after TPA treatments in five of six animals, and in three of six BPO‐treated animals. The MRP/plf‐mRNA species expressed in the skin were predominantly plf1 and mrp3 as determined by gene‐specific restriction enzyme sites within the RT‐PCR products. Expression was either undetectable or found at low levels in acetone‐painted controls and was not detected during the anagen phase of the normal hair growth cycle in unpainted animals. These results demonstrate that mrp/plf‐mRNA is differentially expressed in murine skin in response to mechanistically distinct tumor promoters and has potential utility as a short‐term biomarker for tumor promoting effects in chemical carcinogenesis. © 2005 Government of Canada.