Differentiation-associated overexpression of the cyclin-dependent kinase inhibitor p21waf-1 in human cutaneous squamous cell carcinoma.
p21waf-1 negatively regulates the cell cycle by inhibiting the activity of cyclin-dependent kinases. As p21waf-1 is a probable tumor suppressor, we sought to determine whether this cyclin-dependent kinase inhibitor is abnormally regulated in human cutaneous squamous cell carcinoma (SCC). An immunohistochemical technique was employed to assay p21waf-1 protein in SCCs chosen from sun-exposed and anogenital sites. We observed that p21waf-1 was greatly overexpressed in SCC versus adjacent benign epithelium. Furthermore, expression of p21waf-1 was consistently elevated in the superficial, differentiated cells versus basal keratinocytes. p21waf-1 expression correlated with the proliferative state of the cancers as measured by MIB-1 immunostaining. In vitro, keratinocytes grown in supplemented media upregulated p21waf-1 during differentiation, supporting our in vivo observations. We conclude that p21waf-1 overexpression is associated with differentiation in proliferating SCC but is not sufficient to suppress cancer development.
Tron
V A
VA
Department of Pathology and Laboratory Medicine, Vancouver Hospital and Health Sciences Centre, British Columbia Cancer Research Centre, University of British Columbia, Canada.
Tang
L
L
Yong
W P
WP
Trotter
M J
MJ
D000368:Aged; D002118:Calcium / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D002118:Calcium