Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation.
Exposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer.
Madson
Justin G
JG
Department of Biomedical Sciences, School of Medicine, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA.
Lynch
David T
DT
Tinkum
Kelsey L
KL
Putta
Sumanth K
SK
Hansen
Laura A
LA
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D052160:Benzothiazoles / Q000494:pharmacology; D001665:Binding Sites; D049109:Cell Proliferation; D018925:Chemokines / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D018739:Oncogene Proteins v-erbB / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011855:Radiodermatitis / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000528:radiation effects; D020032:Tyrphostins / Q000494:pharmacology; D014466:Ultraviolet Rays
D052160:Benzothiazoles; D018925:Chemokines; D053583:Interleukin-1beta; D018739:Oncogene Proteins v-erbB; D047428:Protein Kinase Inhibitors; D014157:Transcription Factors; D020032:Tyrphostins; C098214:tyrphostin AG825; D051546:Cyclooxygenase 2