Primary structure of human hepatocellular carcinoma-associated aldehyde dehydrogenase.
Tumor-associated aldehyde dehydrogenase (T-ALDH) is strongly expressed in hepatocellular carcinoma (HCC) but undetectable in normal liver. In the present study, this enzyme from human HCC, HCC T-ALDH, was purified and the partial amino acid sequences (384 residues) determined by direct protein sequencing matched the amino acid sequence (453 residues) deduced from cloned HCC T-ALDH cDNAs with an open reading frame. The coding sequences of HCC T-ALDH cDNA, human stomach ALDH3A1 cDNA [Hsu et al., J. Biol. Chem. 267 (1992) 3030-3037] and human squamous cell carcinoma (SCC) T-ALDH cDNA (Schuuring et al., GenBank I.D. M74542) matched one another except for discrepancies at four positions, with consequent P12R, I27F and S134A substitutions. R and A were found in HCC and SCC T-ALDHs, whereas P and S were present in stomach ALDH3A1. To confirm that these discrepancies would have general occurrence, coding sequences of HCC T-ALDH cDNAs from six patients and stomach ALDH3A1 cDNAs from two individuals were examined and all were found to encode ALDH3A1 having R, I and A at protein positions 12, 27 and 134, respectively, indicating HCC T-ALDH to be variant ALDH3A1 which is common in human stomach tissues.
Satomichi
A
A
Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. satomiti@med.kitasato-u.ac.jp
Nakajima
Y
Y
Takeuchi
A
A
Takagaki
Y
Y
Saigenji
K
K
Shibuya
A
A
D000444:Aldehyde Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D000595:Amino Acid Sequence; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D018076:DNA, Complementary / Q000737:chemistry; D004273:DNA, Neoplasm / Q000737:chemistry; D015723:Gene Library; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology*; D008969:Molecular Sequence Data; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000201:enzymology
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D000444:Aldehyde Dehydrogenase