Overexpression of transcription factor sp2 inhibits epidermal differentiation and increases susceptibility to wound- and carcinogen-induced tumorigenesis.
Sp proteins are evolutionarily conserved transcription factors required for the expression of a wide variety of genes that are critical for development and cell cycle progression. Deregulated expression of certain Sp proteins is associated with the formation of a variety of human tumors; however, direct evidence that any given Sp protein is oncogenic has been lacking. Here, we report that Sp2 protein abundance in mice increases in concert with the progression of carcinogen-induced murine squamous cell carcinomas. Transgenic mice specifically overexpressing murine Sp2 in epidermal basal keratinocytes were highly susceptible to wound- and carcinogen-induced papillomagenesis. Transgenic animals that were homozygous rather than hemizygous for the Sp2 transgene exhibited a striking arrest in the epidermal differentiation program, perishing within 2 weeks of birth. Our results directly support the likelihood that Sp2 overexpression occurring in various human cancers has significant functional effect.
Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina 27606, USA.
Tae-Hyung
TH
Kim
Shannon L
SL
Chiera
Keith E
KE
Linder
Carol S
CS
Trempus
Robert C
RC
Smart
Jonathan M
JM
Horowitz
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D004198:Disease Susceptibility; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D053555:Keratin-5 / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D051704:Sp2 Transcription Factor / Q000502:physiology*; D014947:Wounds and Injuries
D002273:Carcinogens; D053555:Keratin-5; D012333:RNA, Messenger; D051704:Sp2 Transcription Factor; D015127:9,10-Dimethyl-1,2-benzanthracene