Mice lacking the p53/p63 target gene Perp are resistant to papilloma development.
Perp is a target of the p53 tumor suppressor involved in the DNA damage-induced apoptosis pathway. In addition, Perp is a target of the p53-related transcription factor p63 during skin development, where it participates in cell-cell adhesion mediated through desmosomes. Here we test the role of Perp in tumorigenesis in a two-step skin carcinogenesis model system. We find that mice lacking Perp in the skin are resistant to papilloma development, displaying fewer and smaller papillomas than wild-type mice. Proliferation levels, apoptotic indices and differentiation patterns are similar in the skin of treated Perp-deficient and wild-type mice. Instead, impaired adhesion through aberrant desmosome assembly may explain the diminished tumor development in the absence of Perp. These studies indicate that in certain contexts, Perp is required for efficient carcinogenesis and suggest a role for intact cell-cell adhesion in supporting tumor development in these settings.
Marques
Michelle R
MR
Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Horner
Jennifer S
JS
Ihrie
Rebecca A
RA
Bronson
Roderick T
RT
Attardi
Laura D
LD
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002273:Carcinogens; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010212:Papilloma / Q000235:genetics* / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate; D015534:Trans-Activators / Q000235:genetics
D002273:Carcinogens; D008565:Membrane Proteins; C406964:Perp protein, mouse; D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate