Transforming growth factor-beta activities in 'in vivo' lines of hormone-dependent and independent mammary adenocarcinomas induced by medroxyprogesterone acetate in BALB/c mice.
We have determined the presence of transforming growth factor-beta (TGF-beta)-like polypeptides in mammary adenocarcinomas induced by medroxyprogesterone acetate (MPA) in BALB/c mice. In hormone-dependent tumors (HD) from nontreated and MPA-treated mice a high molecular weight (43 kDa) transforming activity was purified by Bio-Gel P-60 chromatography. This TGF was able to confer the neoplastic phenotype on NRK-49F cells without the addition of epidermal growth factor (EGF), though its activity was potentiated by EGF. It did not compete for binding to the EGF receptor, had no mitogenic activity on monolayer cultures of NRK fibroblasts, and was a potent inhibitor of DNA synthesis induced in these cells by EGF and insulin. In HD and hormone-independent tumors (HI) another TGF with a Mr of 13 kDa was isolated. This transforming activity showed the same biological properties as 43 kDa TGF, with the exception that in the absence of EGF it did not stimulate soft agar growth of NRK-49F cells. The synthesis of both factors in 'in vivo' HD tumors seems to be under MPA control, since it is much lower in HD tumors from MPA-treated mice. Further purification of the 13 and 43 kDa TGFs by hydrophobic interaction HPLC demonstrated that each one eluted in a different position, and that their elution profile differed from the TGF-beta from human platelets. The biological activity of the 13 and 43 kDa TGFs was not neutralized by a specific anti-TGF-beta antibody.
Elizalde
P V
PV
Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Lanari
C
C
Kordon
E
E
Tezón
J
J
Charreau
E H
EH
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D002851:Chromatography, High Pressure Liquid; D004261:DNA Replication / Q000187:drug effects; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000633:toxicity; D017258:Medroxyprogesterone Acetate; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000302:isolation & purification* / Q000494:pharmacology; D009376:Neoplasms, Hormone-Dependent / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000302:isolation & purification* / Q000494:pharmacology
D007328:Insulin; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone