Induction of chemokine receptor CXCR4 expression by transforming growth factor-ß1 in human basal cell carcinoma cells.
J Dermatol Sci
; 72(2): 123-33, 2013 Nov.
Article
en En
| MEDLINE
| ID: mdl-23856244
ABSTRACT
BACKGROUND:
Higher CXCR4 expression enhances basal cell carcinoma (BCC) invasion and angiogenesis. The underlying mechanism of increased CXCR4 expression in invasive BCC is still not well understood.OBJECTIVE:
To investigate the mechanisms involved in the regulation of CXCR4 expression in invasive BCC.METHODS:
We used qRT-PCR, RT-PCR, Western blot, and flow cytometric analyses to examine different CXCR4 levels among the clinical samples, co-cultured BCC cells and BCC cells treated with recombinant transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF). Immunohistochemical studies were used to demonstrate the correlation between TGF-ß1 and CXCR4 expressions. The signal transduction pathway and transcriptional regulation were confirmed by treatments with chemical inhibitors, neutralizing antibodies, or short interfering RNAs, as well as luciferase reporter activity.RESULTS:
Invasive BCC has higher TGF-ß1 and CTGF levels compared to non-invasive BCC. Non-contact dermal fibroblasts co-culture with human BCC cells also increases the expression of CXCR4 in BCC cells. Treatment with recombinant human TGF-ß1, but not CTGF, enhanced the CXCR4 levels in time- and dose-dependent manners. The protein level and surface expression of CXCR4 in human BCC cells was increased by TGF-ß1 treatment. TGF-ß1 was intensely expressed in the surrounding fibroblasts of invasive BCC and was positively correlated with the CXCR4 expression of BCC cells. The transcriptional regulation of CXCR4 by TGF-ß1 is mediated by its binding to the TGF-ß receptor II and phosphorylation of the extracellular signal-related kinase 1/2 (ERK1/2)-ETS-1 pathway.CONCLUSION:
TGF-ß1 induces upregulation of CXCR4 in human BCC cells by phosphorylation of ERK1/2-ETS-1 pathway.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
/
Carcinoma Basocelular
/
Regulación Neoplásica de la Expresión Génica
/
Receptores CXCR4
/
Factor de Crecimiento Transformador beta1
Límite:
Humans
Idioma:
En
Revista:
J Dermatol Sci
Asunto de la revista:
DERMATOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Taiwán