The role of KLF4 in UVB-induced murine skin tumor development and its correlation with cyclin D1, p53, and p21(Waf1/Cip1) in epithelial tumors of the human skin.
The zinc-finger-type transcriptional factor KLF4 is expressed in a variety of tissues including skin. KLF4 can function as either a tumor suppressor or an oncogene, depending on the type of tissue in which it is expressed, by modulating the expression of various factors. To understand the role of KLF4 in human skin cancer and also to evaluate the expression of cyclin D1, p53, and p21(Waf1/Cip1) in relation to the expression of KLF4, we evaluated the pattern of KLF4 expression during UVB-induced skin tumor development in SKH-1 hairless mice and in human skin cancer. We also determined whether there are correlations between the expression of KLF4, cyclin D1, p53, and p21 and non-melanoma skin tumors. KLF4 expression was found in the basal layer of non-irradiated control murine skin. Chronic UVB irradiation caused a progressive decrease in KLF4 expression, which was substantially decreased in UVB-induced murine skin tumors. In human precancerous lesions, KLF4 expression was maintained in 64.3% of Bowen's disease samples and 90.0% of AK samples. In contrast, KLF4 expression was significantly reduced in human cancer lesions (p = 0.004). A positive correlation was found between the expression of KLF4 and p21(Waf1/Cip1) in AK, whereas there was a negative correlation between the expression of cyclin D1 and p21(Waf1/Cip1) in Bowen's disease. Thus, our results suggest that KLF4 may function as a tumor suppressor in the skin and that the deregulated expression of KLF4 in the context of p21(Waf1/Cip1) and cyclin D1 expression may be involved in skin tumorigenesis.
Department of Dermatology, Hallym University Sacred Heart Hospital, Pyungchon-dong, Dongan-gu, Anyang, Gyeonggi-do, Republic of Korea.
Woo Jin
WJ
Choi
Sung Hwan
SH
Youn
Jung Ho
JH
Back
Saebomi
S
Park
Eun Joo
EJ
Park
Kwang Joong
KJ
Kim
Hye Rim
HR
Park
Arianna L
AL
Kim
Kwang Ho
KH
Kim
D000818:Animals; D001913:Bowen's Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008812:Mice, Hairless; D012867:Skin / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1