Correlation of TGF-beta 1 expression with medroxyprogesterone acetate responsiveness in mouse mammary adenocarcinomas.
We investigated the expression of transforming growth factors beta 1 and alpha (TGF-beta 1, TGF-alpha) in hormone-responsive (MPA-R) and unresponsive (MPA-U) tumor lines obtained from medroxyprogesterone acetate (MPA)-induced mammary adenocarcinomas in BALB/c mice. The tumors were transplanted into MPA-treated and untreated mice. TGF-beta 1 gene expression was observed in the MPA-R lines growing in untreated animals, but not in MPA-treated mice. TGF-beta 1 mRNA was not detected in the MPA-U tumor lines growing in either MPA-treated or untreated animals. In MPA-R lines the levels of TGF-beta 1 expression were inversely correlated to growth rate. High-affinity TGF-beta 1 receptors were present in the MPA-R tumors. These results suggest that one of the mechanisms by which MPA exerts its proliferative effect on MPA-R tumor lines is inhibition of the expression of TGF-beta 1. Thus, the lack of expression of TGF-beta 1 in MPA-U tumors may be related to the acquisition of autonomous growth.
Elizalde
P V
PV
Instituto de Biología y Medicina Experimental (IBYME) Obligado 2490, Buenos Aires, Argentina.
Guerra
F K
FK
Gravano
M
M
Lanari
C
C
Lippman
M E
ME
Charreau
E H
EH
Lupu
R
R
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D005260:Female; D015870:Gene Expression; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D018125:Receptors, Transforming Growth Factor beta; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D017258:Medroxyprogesterone Acetate