IGF-I-INDUCED IGFBP-3 POTENTIATES THE MITOGENIC ACTIONS OF IGF-I IN MAMMARY EPITHELIAL MD-IGF-I CELLS

被引:31
作者
ROMAGNOLO, D
AKERS, RM
BYATT, JC
WONG, EA
TURNER, JD
机构
[1] VIRGINIA POLYTECH INST & STATE UNIV,DEPT DAIRY SCI,LACTAT PHYSIOL LAB,BLACKSBURG,VA 24061
[2] VIRGINIA POLYTECH INST & STATE UNIV,DEPT ANIM SCI,BIOTECHNOL LAB,BLACKSBURG,VA 24061
[3] MONSANTO AGR CO,ST LOUIS,MO 63198
[4] MCGILL UNIV,DEPT ANIM SCI,MONTREAL 9X 1C0,PQ,CANADA
[5] NIEHS,RES TRIANGLE PK,NC 27709
关键词
INSULIN GROWTH FACTOR I; MITOGENIC ACTION; BINDING PROTEIN;
D O I
10.1016/0303-7207(94)90106-6
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Limited information is available concerning the molecular and cellular mechanisms that regulate expression of insulin-like growth factor-I (IGF-I) binding proteins (IGFBPs) in bovine mammary epithelial cells. Here, we report on the autocrine mechanisms of action of IGF-I and hormonal regulation of expression of IGFBPs in bovine mammary epithelial MD-IGF-I cells which express recombinant IGF-I under the control of the glucocorticoid-inducible mouse mammary tumor virus-long terminal repeat (MMTV-LTR). Levels of IGFBP-3 mRNA and secretion of IGFBP-3 by MD-IGF-I cells were stimulated by IGF-I, insulin (INS), and IGF-I analogs but not prolactin (PRL). Conversely, parental MAC-T cells expressed little IGF-I and secreted primarily IGFBP-2 (29-32 kDa) in response to stimulation with INS, dexamethasone (DEX), or IGF-I analogs. Secretion of recombinant IGF-I caused a 26.5-fold increase in secretion of IGFBP-3, as measured by densitometric analysis of ligand blots, which was associated with a 1.7-fold increase in total DNA. Conditioned media (CM) from MD-IGF-I cells induced with DEX stimulated a 2.8-fold increase in [H-3]thymidine incorporation into DNA of parental MAC-T cells, compared with uninduced cells. Moreover, inclusion of exogenous IGF-I with CM from MD-IGF-I cells triggered an additional 3.0-fold increase in label incorporation, but only a 1.6-fold increase in the presence of IGFBP-2-containing media conditioned by MAC-T cells. Des(1-3)IGF-I added to CM from both MAC-T and MD-IGF-I cells respectively, stimulated a 10.2 and 6.9-fold increase in [H-3]thymidine incorporation into DNA of MAC-T cells. We suggest that expression of IGF-I-induced IGFBP-3 is an important component of an autocrine loop which potentiates the local mitogenic actions of IGF-I in bovine mammary epithelial cells.
引用
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页码:131 / 139
页数:9
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