Overexpression of transcription factor sp2 inhibits epidermal differentiation and increases susceptibility to wound- and carcinogen-induced tumorigenesis.

Abstract

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.

• Authors: Tae-Hyung Kim, Shannon L Chiera, Keith E Linder, Carol S Trempus, Robert C Smart, Jonathan M Horowitz
• Journal: Cancer research (Cancer Res) Vol. 70 Issue 21 Pg. 8507-16 (Nov 01 2010) ISSN: 1538-7445 [Electronic] United States
• PMID: 20959487 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2010 AACR.

Chemical References

• Carcinogens
• Keratin-5
• RNA, Messenger
• Sp2 Transcription Factor
• 9,10-Dimethyl-1,2-benzanthracene

Topics

• 9,10-Dimethyl-1,2-benzanthracene (toxicity)
• Animals
• Blotting, Western
• COS Cells
• Carcinogens (toxicity)
• Carcinoma, Squamous Cell (etiology, metabolism, pathology)
• Cattle
• Cell Differentiation
• Chlorocebus aethiops
• Disease Susceptibility
• Epidermal Cells
• Epidermis (drug effects, metabolism)
• Female
• Humans
• Immunoenzyme Techniques
• Keratin-5 (genetics)
• Keratinocytes (cytology, drug effects, metabolism)
• Male
• Mice
• Mice, Transgenic
• Promoter Regions, Genetic
• RNA, Messenger (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Skin Neoplasms (etiology, metabolism, pathology)
• Sp2 Transcription Factor (physiology)
• Wounds and Injuries