The effect of c-myc on stem cell fate influences skin tumor phenotype.
Nonmelanoma skin cancers (NMSCs) consist of a variety of tumor types including basal cell carcinoma, squamous cell carcinoma, a variety of hair follicle tumors, and sebaceous gland tumors. Genetic alterations that alter the fate of multipotent stem cells are believed to influence NMSC phenotype. We previously generated a transgenic mouse line which constitutively expressed c-myc under the control of the K14 promoter (K14.MYC2). These mice exhibited an increase in size and number of sebaceous glands, suggesting that c-myc diverted multipotential stem cells to a sebaceous lineage. Our goal in the current study was to determine if alterations in the commitment of multipotent stem cells to different cell fates would influence tumor phenotype. To this end, we exposed K14.MYC2 mice to a chemical carcinogenesis protocol and discovered that these mice were predisposed to develop sebaceous adenomas. Our data demonstrate that genetic alterations that alter the fate of multipotent stem cells during embryonic development can markedly influence the phenotype of NMSC that develop following exposure to carcinogens.
Honeycutt
Kimberly A
KA
Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
Waikel
Rebekah L
RL
Koster
Maranke I
MI
Wang
Xiao-Jing
XJ
Roop
Dennis R
DR
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D018266:Adenocarcinoma, Sebaceous / Q000473:pathology; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D006579:Heterozygote; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000473:pathology; D010212:Papilloma / Q000473:pathology; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012626:Sebaceous Gland Neoplasms / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019076:Transgenes
D002273:Carcinogens; D016271:Proto-Oncogene Proteins c-myc; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate