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.
Kim
Tae-Hyung
TH
Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina 27606, USA.
Chiera
Shannon L
SL
Linder
Keith E
KE
Trempus
Carol S
CS
Smart
Robert C
RC
Horowitz
Jonathan M
JM
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