Primary structure of human hepatocellular carcinoma-associated aldehyde dehydrogenase

Tumor-associated aldehyde dehydrogenase (T-ALDH) is strongly expressed in h epatocellular carcinoma (HCC) but undetectable in normal liver. In the pres ent study, this enzyme from human HCC, HCC T-ALDH, was purified and the par tial amino acid sequences (384 residues) determined by direct protein seque ncing matched the amino acid sequence (453 residues) deduced from cloned HC C T-ALDH cDNAs with an open reading frame. The coding sequences of HCC T-AL DH 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 e t ar., 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 stomac h ALDH3Al. To confirm that these discrepancies would have general occurrenc e, coding sequences of HCC T-ALDH cDNAs from six patients and stomach ALDH3 A1 cDNAs from two individuals were examined and all were found to encode AL DH3Al 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 stomac h tissues. (C) 2000 Elsevier Science B.V. All rights reserved.