PMID- 16123117
OWN - NLM
STAT- MEDLINE
DCOM- 20060309
LR  - 20220310
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 27
IP  - 2
DP  - 2006 Feb
TI  - Ultraviolet irradiation induces keratinocyte proliferation and epidermal 
      hyperplasia through the activation of the epidermal growth factor receptor.
PG  - 225-31
AB  - Chronic exposure to ultraviolet (UV) irradiation induces skin cancer, in part, 
      through epigenetic mechanisms that result in the deregulation of cell 
      proliferation. UV irradiation also rapidly activates the epidermal growth factor 
      receptor (EGFR). Since EGFR activation is strongly mitogenic in many cell types 
      including keratinocytes of the skin, we hypothesized that UV-induced cutaneous 
      proliferation results from EGFR activation. The role of EGFR activation in the 
      response of the skin to UV was determined using Egfr-null and Egfr-wild-type skin 
      grafted onto athymic nude mouse hosts, because Egfr-null mice survive only a few 
      days after birth. EGFR was rapidly activated in mouse epidermis following 
      exposure to UV, as detected by the phosphorylation of EGFR on tyrosine residues 
      992, 1045, 1068 and 1173. UV induced epidermal hyperplasia in Egfr-wild-type skin 
      between 48 and 72 h post-UV. However, no epidermal hyperplasia occurred in 
      Egfr-null skin. Baseline cell proliferation was similar in skin grafts of both 
      genotypes. However, UV exposure increased cell proliferation, as measured by Ki67 
      immunohistochemistry and proliferating cell nuclear antigen immunoblotting, 
      maximally at 48 h to a level more than three times higher in wild-type compared 
      with Egfr-null skin. Apoptotic cell death, as measured by terminal 
      deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) analysis, was 
      also increased in UV-exposed Egfr-null skin when compared with wild-type 1-2 days 
      post-UV. These changes in cellular homeostasis after UV were accompanied by 
      increased cyclin D expression in wild-type but not Egfr-null skin and increased 
      expression of p53 and the cyclin-dependent kinase (CDK) inhibitor p21waf1 in 
      Egfr-null skin when compared with wild-type. Collectively, these results 
      demonstrate that the UV-induced activation of EGFR augments keratinocyte 
      proliferation and suppresses apoptosis, leading to epidermal hyperplasia, 
      associated with increased G1 cyclin expression and suppression of CDK inhibitor 
      expression.
FAU - El-Abaseri, Taghrid B
AU  - El-Abaseri TB
AD  - Department of Biomedical Sciences, School of Medicine, Creighton University, 
      Omaha, NE 68178, USA.
FAU - Putta, Sumanth
AU  - Putta S
FAU - Hansen, Laura A
AU  - Hansen LA
LA  - eng
GR  - P20 RR018759/RR/NCRR NIH HHS/United States
GR  - P20 RR018788/RR/NCRR NIH HHS/United States
GR  - 1 CO6 RR17417-01/CO/NCI NIH HHS/United States
GR  - ES-00365-01/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20050825
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (CCNG1 protein, human)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Ccng1 protein, mouse)
RN  - 0 (Cyclin G)
RN  - 0 (Cyclin G1)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cell Proliferation/*radiation effects
MH  - Cyclin G
MH  - Cyclin G1
MH  - Cyclin-Dependent Kinase Inhibitor p21/biosynthesis
MH  - Cyclins/biosynthesis
MH  - ErbB Receptors/*physiology/radiation effects
MH  - Gene Expression Profiling
MH  - Genotype
MH  - Humans
MH  - Hyperplasia
MH  - Immunohistochemistry
MH  - Keratinocytes/*radiation effects
MH  - Mice
MH  - Mice, Nude
MH  - Skin Neoplasms/etiology/genetics/*physiopathology
MH  - Transplantation, Heterologous
MH  - Ultraviolet Rays/*adverse effects
EDAT- 2005/08/27 09:00
MHDA- 2006/03/10 09:00
CRDT- 2005/08/27 09:00
PHST- 2005/08/27 09:00 [pubmed]
PHST- 2006/03/10 09:00 [medline]
PHST- 2005/08/27 09:00 [entrez]
AID - bgi220 [pii]
AID - 10.1093/carcin/bgi220 [doi]
PST - ppublish
SO  - Carcinogenesis. 2006 Feb;27(2):225-31. doi: 10.1093/carcin/bgi220. Epub 2005 Aug 
      25.