Modulation of transforming growth factor beta1 gene expression in the mammary gland by insulin-like growth factor I and octreotide.
Document Type
Article
Publication Date
2000
Keywords
Antineoplastic-Agents-Hormonal, Breast, Female, Human, Insulin-Like-Growth-Factor-I, Mice, Mice-Inbred-C57BL, Octreotide, RNA-Messenger, SUPPORT-NON-U-S-GOVT, Transforming-Growth-Factor-beta
First Page
277
Last Page
281
JAX Source
Int J Oncol 2000 Feb; 16(2):277-81.
Abstract
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.
Recommended Citation
Huynh H,
Beamer W,
Pollak M,
Chan TW.
Modulation of transforming growth factor beta1 gene expression in the mammary gland by insulin-like growth factor I and octreotide. Int J Oncol 2000 Feb; 16(2):277-81.