Open AccessInduction of ErbB2 by ultraviolet A irradiation: Potential role in malignant transformation of keratinocytes
Author(s) -
Han Chang Yeob,
Lim Sung Chul,
Choi Hong Seok,
Kang Keon Wook
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00718.x
Subject(s) - transformation (genetics) , ultraviolet irradiation , malignant transformation , cancer research , ultraviolet radiation , irradiation , ultraviolet , keratinocyte , ultraviolet a , medicine , chemistry , biology , dermatology , cell culture , optoelectronics , materials science , genetics , physics , radiochemistry , gene , nuclear physics
Ultraviolet (UV) A (320–400 nm), which constitutes more than 90% of UV radiation in the sunlight that reaches the earth's surface, is considered a major cause of human skin photo‐aging and skin cancer. Exposure of keratinocytes to UVA has previously been reported to lead to the activation of a variety of epidermal growth factor receptors (EGFR), including ErbB2, and ErbB2 activation is involved in skin tumor development. Here, we demonstrate that ErbB2 expression is enhanced by low‐energy UVA (300–3000 mJ/cm 2 ) irradiation in the skin tissues of both hairless mice and HaCaT keratinocytes. Luciferase reporter‐gene activity using the 756‐bp flanking region of the human erbB2 gene was increased by UVA irradiation. UVA irradiation also selectively increased the levels of activator protein (AP)‐2α, but not AP‐2β and AP‐2γ. The increase in the reporter gene activity of HaCaT cells exposed to UVA was abolished by mutation of the two AP‐2 binding sites in the promoter region of the erbB2 gene. Inhibition of cAMP‐dependent protein kinase caused complete blockage of ErbB2 induction and AP‐2α activation by UVA irradiation. Finally, we reveal that pre‐exposure of HaCaT cells to UVA potentiates EGF‐inducible anchorage‐independent growth of the keratinocytes, which is significantly suppressed by ErbB2 inhibition. These results support the hypothesis that UVA enhances the expression of ErbB2 via cAMP‐ and protein kinase‐dependent AP‐2α activation in keratinocytes, which may serve as a key mechanistic basis for the malignant transformation of keratinocytes exposed to UVA irradiation. ( Cancer Sci 2008; 99: 502–509)