Modulation of transforming growth factor beta1 gene expression in the mammary gland by insulin-like growth factor I and octreotide.
Transforming growth factor beta1 (TGF-beta1) has been shown to exhibit anti-proliferative activity for mammary gland epithelial cells and for human breast cancer cells. Insulin-like growth factor I (IGF-I), in contrast, is a well-characterized mitogenic and anti-apoptotic factor involved in mammary gland physiology. In order to examine the hypothesis that IGF-I suppresses TGF-beta1 expression in the mammary gland, we studied the effect of various manipulations of the growth hormone - IGF-I axis on TGF-beta1 mRNA abundance. Administration of IGF-I to intact animal suppressed TGF-beta1 mRNA levels in a dose-dependent manner to approximately 20% of control levels. Administration of the somatostatin analogue octreotide in a manner previously shown to acutely suppress the growth hormone - IGF-I axis increased mammary gland TGF-beta1 expression approximately 3-fold. Transgenic mice overexpressing growth hormone expressed TGF-beta1 in the mammary gland at only approximately 12% of the level of control animals, while mice IGF-I deficient due to the mutation expressed TGF-beta1 at slightly higher levels than control animals. The large differences in TGF-beta1 expression between control and GH-transgenic animals were correlated with major differences in architecture of the mammary gland, while the appearance of mammary glands of normal and animals was similar. These data document a previously unrecognized relationship between TGF-beta1 and IGF-I physiology in the mammary gland, and suggest a novel mechanism by which somatostatin analogues influence the proliferative behaviour of breast epithelial cells.
Huynh
H
H
Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre of Singapore, Singapore 169610, Republic of Singapore.
Beamer
W
W
Pollak
M
M
Chan
T W
TW
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015282:Octreotide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D015282:Octreotide