Human promyelocytic cell line HL60 has the specific binding sites for prolactin and its ornithine decarboxylase, DNA synthesis and cellular proliferation are induced by prolactin.
Human prolactin (hPRL) induced ornithine decarboxylase (ODC) activity, subsequently DNA synthesis and cellular proliferation on human promyelocytic cells, HL60, cultured in a serum-free medium. HL60 cells had 2100 specific binding sites for hPRL per cell, showing a dissociation constant of 1.1 x 10(-10) M. Binding of 125I-PRL to the cells was not blocked by simultaneous addition of human growth hormone. ODC activity and DNA synthesis were activated maximally at 5 and 20 h, respectively, after the addition of 0.05 nM hPRL. These effects of PRL on cellular proliferation, ODC activity and DNA synthesis were abolished by the simultaneous addition of anti-hPRL antibody. Simultaneous addition of an irreversible inhibitor of ODC, difluoromethyl ornithine (DFMO), also abolished the inductions of ODC and DNA synthesis by hPRL. The inhibitory effect of DFMO on hPRL-induced DNA synthesis was reversed by the addition of putrescine to the culture medium. These results suggest that hPRL binds to the prolactin receptor on HL60 cells and induces ODC activity to increase cellular polyamine levels, which eventually stimulates DNA synthesis and cellular proliferation.
Nishiguchi
Y
Y
Department of Biochemistry, Mie University Faculty of Medicine, Japan.
Hibasami
H
H
Komada
Y
Y
Sakurai
M
M
Nakashima
K
K
D001665:Binding Sites; D002250:Carbon Radioisotopes; D002455:Cell Division / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D011388:Prolactin / Q000378:metabolism / Q000494:pharmacology*; D011981:Receptors, Prolactin / Q000096:biosynthesis*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D002250:Carbon Radioisotopes; D004273:DNA, Neoplasm; D007457:Iodine Radioisotopes; D011981:Receptors, Prolactin; D014316:Tritium; D011388:Prolactin; D009955:Ornithine Decarboxylase; D013936:Thymidine