An inhibitor of the epidermal growth factor receptor function does not affect the ability of human papillomavirus 11 to form warts in the xenografted immunodeficient mouse model.
Epidermal growth factor receptor (EGFr) has been shown to be induced and activated in cells infected with HPV, suggesting that it may play a physiological role in viral replication or in the formation or maintenance of warts. To investigate this possibility, human foreskin tissue was infected with HPV11 and transplanted onto the renal capsule and the dermis of immunodeficient mice. The animals were treated orally or topically with the potent EGFr inhibitor CP-545130, with treatment starting either immediately following graft attachment, or following a 70 day period to allow development of warts. The rate of appearance of warts, wart size and number were monitored. In addition, we measured intra-lesional HPV replication levels and examined the morphology of the graft tissues. Analysis of the results showed no significant difference between placebo and compound-treated groups, despite high levels of compound present in the graft tissue. We conclude that EGFr kinase activity is not required for the development and maintenance of HPV-11-induced warts in this model.
Parkinson
Tanya
T
Pfizer Global Research & Development, Sandwich, Kent, UK. tanya.parkinson@pfizer.com
Howett
Mary K
MK
Welsh
Patricia A
PA
Patrick
Susan D
SD
Neely
Elizabeth B
EB
Flanagan
Neil
N
Pollack
Vincent A
VA
Pustilnik
Leslie R
LR
Moyer
Jim
J
Perros
Manos
M
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000502:physiology; D005260:Female; D052140:Human papillomavirus 11 / Q000502:physiology; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011799:Quinazolines / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D014412:Tumor Virus Infections / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects*; D014860:Warts / Q000821:virology*
D004791:Enzyme Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors