Modulation of transforming growth factor beta1 gene expression in the mammary gland by insulin-like growth factor I and octreotide.
Modulation of transforming growth factor beta1 gene expression in the mammary gland by insulin-like growth factor I and octreotide.
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胰岛素样生长因子 I 和奥曲肽对乳腺转化生长因子 β1 基因表达的调节。
DOI：
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发表时间：
2000
影响因子：
5.2
通讯作者：
T. Chan
中科院分区：
文献类型：
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作者：
Hung Huynh;W. Beamer;Michael Pollak;T. Chan
转化生长因子β1(TGF-β1)对乳腺上皮细胞和人乳腺癌细胞具有抗增殖活性。相反，胰岛素样生长因子I(IGF-I)是一种与乳腺生理有关的促有丝分裂和抗凋亡因子。为了验证胰岛素样生长因子-I抑制转化生长因子-β1在乳腺中表达的假说，我们研究了生长激素-胰岛素样生长因子-I轴的各种操作对转化生长因子-β1基因丰度的影响。给予完整动物的IGF-I以剂量依赖的方式抑制转化生长因子-β1的mRNA水平，约为对照水平的20%。给予生长抑素类似物奥曲肽可以显著抑制生长激素-IGF-I轴的表达，使乳腺转化生长因子-β1的表达增加约3倍。过量表达生长激素的转基因小鼠在乳腺中的表达水平仅为对照动物的约12%，而由于突变而导致的IGF-I缺陷小鼠的表达水平略高于对照动物。对照组和GH转基因动物的转化生长因子-β1表达的巨大差异与乳腺结构的主要差异有关，而正常和动物的乳腺外观相似。这些数据证明了乳腺中转化生长因子-β1和胰岛素样生长因子-I生理学之间以前未知的关系，并提示了生长抑素类似物影响乳腺上皮细胞增殖行为的新机制。
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.