Growth regulatory peptide production by human breast carcinoma cells.
The mechanisms by which human breast cancers regulate their own growth have been studied by us in an in vitro model system. We showed that specific growth factors (IGF-I, TGF alpha, PDGF) are secreted by human breast cancer cells. A variety of experiments suggest that they are involved in tumor growth and progression. These activities are induced by estradiol in hormone-dependent breast cancer cells and secreted constitutively by estrogen-independent cells. Concentrates of conditioned medium derived from breast cancer cells can induce the growth of hormone-dependent cells in vivo in athymic nude mice. Hormone-dependent breast cancer cells also secrete TGF beta. TGF beta is growth inhibitory. Growth inhibitors such as antiestrogens or glucocorticoids increase TGF beta secretion. An antiestrogen-resistant mutant of MCF-7 cells does not secrete TGF beta when treated with antiestrogen, but is growth inhibited when treated with exogenous TGF beta. Thus, TGF beta functions as a negative autocrine growth regulator and is probably responsible for some of the growth inhibitory effects of antiestrogens.
Lippman
M E
ME
Medical Breast Cancer Section, National Cancer Institute, Bethesda, MD 20892.
Dickson
R B
RB
Gelmann
E P
EP
Rosen
N
N
Knabbe
C
C
Bates
S
S
Bronzert
D
D
Huff
K
K
Kasid
A
A
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D010452:Peptide Biosynthesis; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D015291:Transforming Growth Factors
D004965:Estrogen Antagonists; D004967:Estrogens; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D007334:Insulin-Like Growth Factor I; D015291:Transforming Growth Factors