[Growth hormones and oncogenes in mammary adenocarcinomas induced by medroxyprogesterone acetate in BALB/c mice].
We have studied the involvement of growth factors (GF), their receptors (GF-R) and oncogenes in modulating tumor growth in the medroxyprogesterone acetate (MPA)-induced mammary tumor model in BALB/c mice. We demonstrated the presence of both ligands of the insulin-like growth factor family (IGF-I, IGF-II) and the two types of receptors (IGF-RI, IGF-RII). MPA upregulated IGF-II mRNA and protein levels in hormone-dependent lines (MPA-D). The progression to a hormone-independent phenotype was accompanied by a high constitutive expression of IGF-II and by a significant decrease in IGF-IIR number. An antisense strategy used to evaluate the role of IGF in the MPA-induced growth of epithelial MPA-D cells showed that IGF mediate progestin-induced mammary tumor growth by autocrine/intracrine pathways. We also studied the role of heregulins (HRG), the recently identified ligands for the c-erbB3 and c-erbB4 oncogenes. HRG mRNA expression was restricted to tumors of ductal origin. MPA induced an in vivo up-regulation of HRG expression. Finally, we also found that MPA may be exerting its proliferative effect on MPA-D lines by inhibiting the expression of transforming growth factor beta 1, (TGF-beta 1) and the lack of expression of TGF-beta 1 in hormone-independent tumors may be related to the acquisition of autonomous growth.
Elizalde
P V
PV
Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Balaña
M E
ME
Charreau
E H
EH
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000032:analysis; D005260:Female; D006133:Growth Substances / Q000032:analysis*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate; D051379:Mice; D008807:Mice, Inbred BALB C; D009857:Oncogenes / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000032:analysis
D006133:Growth Substances; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017258:Medroxyprogesterone Acetate
Factores de crecimiento y oncogenes en adenocarcinomas mamarios inducidos por acetato de medroxyprogesterona en ratones BALB/c.