The nucleotide sequence of Hs 3-PGDH gene, encoding human 3-phosphoglycerat
e dehydrogenase that catalyzes the initiating step in the phosphorylated pa
thway of serine biosynthesis, has been determined, The 3-PGDH gene has a pr
edicted 533 amino acid open reading frame, encoding a 56.8 kDa protein that
shares 94.0% similarity with rat-liver 3-PGDH, Two different transcripts c
orresponding to 3-PGDH mRNA were detected in human normal tissues. A domina
nt 2.1 kb transcript was expressed at high levels in prostate. testis, ovar
y, brain, liver, kidney, and pancreas, and weakly expressed in thymus, colo
n, and heart. A 710 bp transcript also appeared as a weaker band where the
2.1 kb mRNA was expressed, and it was more significant than the 2.1 kb mRNA
in heart and skeletal muscle. The TPA-induced monocytic differentiation of
U937, which also resulted in growth arrest, abruptly downregulated the exp
ression of 3-PGDH. Removal of TPA restored cell growth through the retrodif
ferentiation process and subsequent expression of 3-PGDH. The 3-PGDH mRNA w
as markedly expressed in human leukemias, lymphoma Sup-T1, colon adenocarci
noma COLO 320DM, epitheloid carcinoma HeLa S3, and murine lymphoma BW5147.G
.1.4, but not in human leukemia K562, This report demonstrates that the hum
an 3-PGDH-gene is regulated at the transcriptional level depending on tissu
e specificty and cellular proliferative status, and its transcriptional reg
ulation mechanism may be a useful target for diagnosis and therapy of cance
r. (C) 2000 Elsevier Science B.V. All rights reserved.