CUSP/p63 expression in basal cell carcinoma.
Chronic ulcerative stomatitis protein (CUSP), the most abundant cutaneous isoform of p63, is a p53-related gene essential for epithelial development. CUSP lacks the N-terminal transactivation domain found on other p53 family members and has been shown to inhibit p53 function in vitro. In this study, biopsies of normal skin (21 of 21), benign neoplasms [seborrheic keratosis (3 of 3), acrochordon (2 of 3), and verruca plana (3 of 3)], and squamous cell carcinomas (SCC) (4 of 4) displayed strong nuclear CUSP immuno-reactivity in epidermal cells. In contrast few basal cell carcinomas (BCC) (7 of 27) and sebaceous nevi (1 of 2) displayed this pattern of CUSP immunoreactivity. Thus, biopsies of cutaneous conditions characterized by sonic hedgehog (SHH) pathway dysregulation were more than 86 times as likely to lack CUSP/p63 immunofluorescence as were other cutaneous samples. Adjacent normal-appearing skin from patients with basal cell nevus syndrome (BCNS) (2 of 3) also lacked CUSP immuno-staining. Lastly, a BCC arising in a patched heterozygous mouse also lacked CUSP immuno-staining. Because CUSP mRNA and protein were detected via Northern and Western analysis in BCC samples lacking CUSP immuno-staining, we sequenced the coding region of CUSP from two non-staining BCCs but found no mutations. Therefore, CUSP appears to be present, unmutated, and yet frequently undetectable by immunofluorescence in cutaneous lesions in both humans and mice that are associated with SHH pathway dysregulation (BCCs, BCNS, and nevus sebaceous).
Dellavalle
Robert P
RP
Department of Dermatology, University of Colorado School of Medicine, Denver, Colorado, USA.
Walsh
Patrick
P
Marchbank
Angela
A
Grayson
Timothy E
TE
Su
Lih-Jen
LJ
Parker
Eva R
ER
DeGregori
James
J
Penheiter
Kristi
K
Aszterbaum
Michelle
M
Epstein
Ervin H
EH
Lee
Lela A
LA
D000818:Animals; D001478:Basal Cell Nevus Syndrome / Q000235:genetics / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins; D005455:Fluorescent Antibody Technique; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics*; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D012334:RNA, Neoplasm; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; D025521:Tumor Suppressor Proteins