Aminopeptidase A expression and enzymatic activity in primary human renal cancers.
The gp160 human kidney differentiation antigen is identical to human aminopeptidase A (APA), a zinc-dependent cell-surface metallopeptidase which hydrolyzes peptides with N-terminal acidic residues. GP160/APA is constitutively expressed by proximal tubule cells, the normal cellular counterpart of most renal cancers (RCs). Immunohistochemical analysis of gp160/APA protein expression in 62 primary renal tumor specimens using monoclonal antibody S4 revealed heterogeneous or homogeneous expression of gp160/APA in 46/51 (90%) of clear cell carcinomas in contrast with 1/8 (13%) papillary renal tumors and 0/3 oncocytomas (p<0.001). Analysis of five primary clear cell carcinomas for gp160 protein expression immunohistochemically and associated APA catalytic activity revealed one tumor which expressed gp160/APA protein which was enzymatically inactive. Direct sequence analysis of DNA derived from this specimen could not detect mutations within the zinc-binding domain which would eliminate gp160/APA catalytic activity. These data indicate that the gp160/APA protein is expressed by primary clear cell but not papillary RCs or oncocytomas, and that alterations in gp160/APA protein including loss of protein expression or enzymatic activity occur in 20% of primary clear cell RCs.
Genitourinary Oncology Research Laboratory, Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, New York Hospital-Cornell University Medical Center, NY 10021, USA.
D M
DM
Nanus
T
T
Bogenrieder
C N
CN
Papandreou
C L
CL
Finstad
A
A
Lee
V
V
Vlamis
R J
RJ
Motzer
N H
NH
Bander
A P
AP
Albino
V E
VE
Reuter
D018249:Adenoma, Oxyphilic / Q000201:enzymology / Q000473:pathology; D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000201:enzymology / Q000473:pathology; D004273:DNA, Neoplasm / Q000378:metabolism; D043384:Glutamyl Aminopeptidase; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase