E2F7 can regulate proliferation, differentiation, and apoptotic responses in human keratinocytes: Implications for cutaneous squamous cell carcinoma formation

Endo-Munoz, Liliana, Dahler, Alison, Teakle, Ngari, Rickwood, Danny, Hazar-Rethinam, Mehlika, Abdul-Jabbar, Ibtissam, Sommerville, Scott, Dickinson, Ian, Kaur, Pritinder, Paquet-Fifield, Sophie and Saunders, Nicholas (2009) E2F7 can regulate proliferation, differentiation, and apoptotic responses in human keratinocytes: Implications for cutaneous squamous cell carcinoma formation. Cancer Research, 69 5: 1800-1808. doi:10.1158/0008-5472.CAN-08-2725


Author Endo-Munoz, Liliana
Dahler, Alison
Teakle, Ngari
Rickwood, Danny
Hazar-Rethinam, Mehlika
Abdul-Jabbar, Ibtissam
Sommerville, Scott
Dickinson, Ian
Kaur, Pritinder
Paquet-Fifield, Sophie
Saunders, Nicholas
Title E2F7 can regulate proliferation, differentiation, and apoptotic responses in human keratinocytes: Implications for cutaneous squamous cell carcinoma formation
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
1538-7445
Publication date 2009-03
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-08-2725
Volume 69
Issue 5
Start page 1800
End page 1808
Total pages 9
Editor F. J. Rauscher III
Place of publication Philadelphia, PA, U.S.A.
Publisher American Association for Cancer Research
Collection year 2010
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
970111 Expanding Knowledge in the Medical and Health Sciences
920117 Skin and Related Disorders
1112 Oncology and Carcinogenesis
Formatted abstract
The E2F family of transcription factors plays a crucial role in the regulation of genes involved in cell proliferation, differentiation, and apoptosis. In keratinocytes, the inhibition of E2F is a key step in the control and initiation of squamous differentiation. Because the product of the recently identified E2F7a/E2F7b gene has been shown to repress E2F-regulated promoters, and to be abundant in skin, we examined its role in the epidermis. Our results indicate that E2F7b mRNA expression is selectively associated with proliferation-competent keratinocytes. Moreover, E2F7 was able to antagonize E2F1-induced proliferation and apoptosis. In contrast, although E2F7 was able to inhibit proliferation and initiate differentiation, it was unable to antagonize the differentiation suppression induced by E2F1. These data indicate that E2F7-mediated suppression of proliferation and apoptosis acts through E2F1-dependent pathways, whereas E2F7-induced differentiation acts through an E2F1-independent pathway. These data also suggest that proliferation, differentiation, and survival of primary human keratinocytes can be controlled by the relative ratio of E2F1 to E2F7. Because deregulated proliferation, differentiation, and apoptosis are hallmarks of cancer, we examined the expression levels of E2F1 and E2F7 in cutaneous squamous cell carcinomas (CSCC). We found that both genes were overexpressed in CSCCs compared with normal epidermis. Furthermore, inhibition of E2F7 in a SCC cell line sensitized the cells to UV-induced apoptosis and doxorubicin-induced apoptosis. Combined, these data suggest that the selected disruption of E2F1 and E2F7 in keratinocytes is likely to contribute to CSCC formation and may prove to be a viable therapeutic target.
Keyword Keratinocytes
Cutaneous
Carcinoma
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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Created: Thu, 03 Sep 2009, 08:34:26 EST by Mr Andrew Martlew on behalf of UQ Diamantina Institute