Document Detail


Deficiency of the Kruppel-like factor KLF4 correlates with increased cell proliferation and enhanced skin tumorigenesis.
MedLine Citation:
PMID:  22491752     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Kruppel-like factor 4 (KLF4) is a transcription factor that is highly expressed in differentiated epithelial cells including that of the skin. It is critical for specification or function of differentiated epithelial cells. Moreover, KLF4 functions either as a tumor suppressor or an oncogene depending on different cellular contexts. However, the role of KLF4 in skin tumorigenesis remains controversial. To address this issue, we first examined KLF4 expression using a cohort of samples from patients with skin squamous cell carcinoma and basal cell carcinoma and found that in 21 of 24 tumor tissues (87.5%), KLF4 expression as assayed by immunohistochemistry was absent when compared with that in normal tissues. In addition, knockdown of KLF4 in human epidermal squamous cell carcinoma SCC13 cells was accompanied by increased cell growth. Further analysis revealed that KLF4 deficiency promoted cell migration and adhesion, which are the important properties of tumor cells. These observations were supported by the effect upon overexpression of KLF4 in SCC13 cells. Furthermore, we generated a novel tamoxifen-inducible KLF4/CreER and KLF4(flox) double transgenic mouse model to examine the role of KLF4 in skin cancer development. Consistent with in vitro studies, KLF4 deficiency increased the ability of migration and adhesion of mouse primary skin keratinocytes. Moreover, KLF4 knockout led to increased cell proliferation and skin carcinogenesis in a classical DMBA/TPA mouse skin cancer model. Taken together, our data suggest that KLF4 inhibits cell proliferation, migration and adhesion and that loss of KLF4 promotes skin tumorigenesis.
Authors:
Juan Li; Hai Zheng; Fang Yu; Tianxin Yu; Chunming Liu; Shiang Huang; Timothy C Wang; Walden Ai
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-09
Journal Detail:
Title:  Carcinogenesis     Volume:  33     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-07-04     Completed Date:  2012-09-17     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  1239-46     Citation Subset:  IM    
Affiliation:
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, 29208, USA.
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MeSH Terms
Descriptor/Qualifier:
9,10-Dimethyl-1,2-benzanthracene
Animals
Carcinoma, Basal Cell / genetics,  metabolism*,  pathology
Carcinoma, Squamous Cell / genetics,  metabolism*,  pathology
Cell Adhesion / genetics
Cell Differentiation
Cell Movement / genetics
Cell Proliferation
Cell Transformation, Neoplastic
Cells, Cultured
Female
Gene Expression Regulation, Neoplastic
Humans
Keratinocytes / metabolism
Kruppel-Like Transcription Factors / deficiency*,  genetics,  metabolism*
Mice
Mice, Transgenic
RNA Interference
RNA, Small Interfering
Skin Neoplasms / chemically induced,  metabolism*,  pathology*
Tamoxifen / pharmacology
Tetradecanoylphorbol Acetate
Grant Support
ID/Acronym/Agency:
1K01DK069489/DK/NIDDK NIH HHS; 1R03AR060987/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/GKLF protein; 0/Kruppel-Like Transcription Factors; 0/RNA, Small Interfering; 10540-29-1/Tamoxifen; 16561-29-8/Tetradecanoylphorbol Acetate; 57-97-6/9,10-Dimethyl-1,2-benzanthracene
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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