Decreased mRNA expression of several basement membrane components in basal cell carcinoma.
The biologic factors that control the behavior of basal cell carcinoma are poorly understood. This study was undertaken to elucidate the mechanisms responsible for the altered protein levels of several basement membrane components found in basal cell carcinoma. RNA was isolated from papulonodular basal cell carcinoma, normal human epidermal keratinocytes, and normal human skin, reverse transcribed to cDNA and amplified by the polymerase chain reaction utilizing primers specific for the 230 kDa bullous pemphigoid antigen (BPAG1), the 180 kDa bullous pemphigoid antigen (BPAG2), the alpha6 and beta4 chains of the alpha6beta4 integrin complex, and the beta3 chain of laminin 5. Southern blots probed with internal oligonucleotides confirmed that each polymerase chain reaction was specific for the basement membrane component amplified. The mRNA expressions of basement membrane components were indistinguishable between normal human epidermal keratinocytes and normal human skin, and subsequent experiments used normal human epidermal keratinocytes as controls. Quantitation of polymerase chain reaction products indicated that all basement membrane specific mRNA were significantly decreased in basal cell carcinoma as compared with normal human epidermal keratinocytes. The mean polymerase chain reaction product intensities were significantly less in the basal cell carcinoma as compared with the normal human epidermal keratinocytes at the following levels: p < 0.001 for alpha6 and beta4 integrins and the beta3 chain of laminin 5; p < 0.01 for BPAG1; and p < 0.05 for BPAG2. Our results demonstrate that decreased protein levels of basement membrane components in basal cell carcinoma are due at least partially to a downregulation of basement membrane mRNA species. We speculate that these alterations may lead to a structurally incompetent basement membrane that facilitates the basal cell carcinoma ability to invade tissues.
Chopra
A
A
Department of Dermatology, Skin Diseases Research Center, Case Western Reserve University, University Hospitals of Cleveland, Ohio 44106, USA.
Maitra
B
B
Korman
N J
NJ
D015703:Antigens, CD; D001324:Autoantigens / Q000032:analysis; D001485:Basement Membrane / Q000737:chemistry*; D015139:Blotting, Southern; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003094:Collagen; D046508:Culture Techniques; D003598:Cytoskeletal Proteins; D003896:Desmosomes / Q000737:chemistry / Q000378:metabolism; D000071821:Dystonin; D006801:Humans; D039503:Integrin alpha6; D039663:Integrin beta4; D015603:Keratinocytes / Q000737:chemistry; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase; D012867:Skin / Q000737:chemistry; D000097794:Kalinin; D000097805:Collagen Type XVII
D015703:Antigens, CD; D001324:Autoantigens; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D039503:Integrin alpha6; D039663:Integrin beta4; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase; D000097794:Kalinin; D000097805:Collagen Type XVII; C486268:DST protein, human