E2F-1 induces proliferation-specific genes and suppresses squamous differentiation-specific genes in human epidermal keratinocytes

Dicker, Anthony J., Popa, Claudia, Dahler, Alison L., Serewko, Magdelena M., Hilditch-Maguire, Paige A., Frazer, Ian H. and Saunders, Nicholas A. (2000) E2F-1 induces proliferation-specific genes and suppresses squamous differentiation-specific genes in human epidermal keratinocytes. Oncogene, 19 25: 2887-2894. doi:10.1038/sj.onc.1203610


Author Dicker, Anthony J.
Popa, Claudia
Dahler, Alison L.
Serewko, Magdelena M.
Hilditch-Maguire, Paige A.
Frazer, Ian H.
Saunders, Nicholas A.
Title E2F-1 induces proliferation-specific genes and suppresses squamous differentiation-specific genes in human epidermal keratinocytes
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
1476-5594
Publication date 2000-06-08
Sub-type Article (original research)
DOI 10.1038/sj.onc.1203610
Volume 19
Issue 25
Start page 2887
End page 2894
Total pages 8
Place of publication London, United Kingdom
Publisher Nature
Language eng
Abstract Squamous differentiation of keratinocytes is associated with decreases in E2F-1 mRNA expression and E2F activity, and these processes are disrupted in squamous cell carcinoma cell lines. We now show that E2F-1 mRNA expression is increased in primary squamous cell carcinomas of the skin relative to normal epidermis, To explore the relationship between E2F-1 and squamous differentiation further, we examined the effect of altering E2F activity in primary human keratinocytes induced to differentiate. Promoter activity for the proliferation-associated genes, cdc2 and keratin 14, are inhibited during squamous differentiation. This inhibition can be inhibited by overexpression of E2F-1 in keratinocytes, Overexpression of E2F-1 also suppressed the expression of differentiation markers (transglutaminase type 1 and keratin 10) in differentiated keratinocytes, Blocking E2F activity by transfecting proliferating keratinocytes with dominant negative E2F-1 constructs inhibited the expression of cdc2 and E2F-1, but did not induce differentiation. Furthermore, expression of the dominant negative construct in epithelial carcinoma cell lines and normal keratinocytes decreased expression from the cdc2 promoter. These data indicate that E2F-1 promotes keratinocyte proliferation-specific marker genes and suppresses squamous differentiation-specific marker genes. Moreover, these data indicate that targeted disruption of E2F-1 activity may have therapeutic potential for the treatment of squamous carcinomas.
Keyword Carcinogenesis
E2F-1
Differentiation
Keratinocyte
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Diamantina Institute - Open Access Collection
UQ Diamantina Institute Publications
 
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Created: Mon, 13 Aug 2007, 11:47:54 EST