Human fibroblasts (KMST-6/RAS line) transformed with 60Co gamma-rays and c-Ha-ras oncogene constitutively produce a large amount of human granulocyte-colony stimulating factor (G-CSF).
Human fibroblasts (KMST-6/RAS) transformed with 60Co gamma-rays and the Ha-ras oncogene formed tumors in nude mice. These mice showed splenomegaly and an increase in granulocytes in the peripheral blood. There was a direct correlation between tumor size and spleen size. Histologically, prominent proliferation of granulocytes was observed in the enlarged spleen. These findings indicated that KMST-6/RAS cells might have been producing granulocyte colony-stimulating factor (G-CSF) in the nude mice. In fact, in vitro studies demonstrated that the cells produced G-CSF in the culture medium and that production of G-CSF was greater during the logarithmic growth than during the stationary phase. Nearly equal amounts of G-CSF were produced by cells grown in serum-free or 10% serum-supplemented medium. Neither expression of the ras oncogene nor the tumorigenicity of cells correlated with the production of G-CSF. G-CSF production in KMST-6/RAS cells was significantly stimulated by butyrate, but not by dexamethasone or 5-azacytidine.
Kawashima
K
K
Department of Cell Biology, Okayama University Medical School.
Mori
M
M
Furusako
S
S
Usuki
H
H
Namba
M
M
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003037:Cobalt Radioisotopes; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D005720:Gamma Rays; D011905:Genes, ras; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000209:etiology
D002087:Butyrates; D003037:Cobalt Radioisotopes; D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone; D001374:Azacitidine