Effects of endogenous insulin-like growth factor binding protein-3 on cell cycle regulation in breast cancer cells.

High tissue insulin-like growth factor binding protein-3 (IGFBP-3) expression in breast cancers is associated in some studies with rapid growth and poor outcome. This study examined the effects of endogenous IGFBP-3 in Hs578T breast cancer cells, which are IGF-unresponsive and grow aggressively despite relatively high IGFBP-3 expression. IGFBP-3 downregulation using siRNA was associated with increases in DNA synthesis, the percentage of cells in S phase and viable cell numbers, accompanied by increases in cyclins A and D1, a decrease in p27 expression, and increased phosphorylation of retinoblastoma (Rb) on Ser795.

Molecular basis of the interaction between IGFBP-3 and retinoid X receptor: role in modulation of RAR-signaling.

IGFBP-3 interacts with the retinoid X receptor-alpha (RXRalpha) and retinoic acid receptor-alpha (RARalpha) and thereby interferes with the formation of RXR:RAR heterodimers. Here we identify the domains in RXRalpha and IGFBP-3 that participate in this interaction. When different regions of RXRalpha were expressed independently, we found that only the DNA-binding domain (C-domain) bound IGFBP-3.

Insulin-like growth factor binding protein-5 interacts with the vitamin D receptor and modulates the vitamin D response in osteoblasts.

The 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]-induced differentiation of osteoblasts comprises the sequential induction of cell cycle arrest at G0/G1 and the expression of bone matrix proteins. Reports differ on the effects of IGF binding protein (IGFBP)-5 on bone cell growth and osteoblastic function. IGFBP-5 can be growth stimulatory or inhibitory and can enhance or impair osteoblast function.

Insulin-like growth factor binding protein-3 prevents retinoid receptor heterodimerization: implications for retinoic acid-sensitivity in human breast cancer cells.

Insulin-like growth factor binding protein-3 (IGFBP-3) has both IGF-dependent and -independent effects on cell growth, which are frequently growth-inhibitory. Interestingly, the development of a more aggressive phenotype in breast cancer cells (BCCs) correlates positively with elevated expression of IGFBP-3 and is often associated with all-trans-retinoic acid (atRA)-resistance. IGFBP-3 was previously demonstrated to interact directly with retinoid X receptor (RXR).