PMID- 9735418 OWN - NLM STAT- MEDLINE DCOM- 19981209 LR - 20190516 IS - 1019-6439 (Print) IS - 1019-6439 (Linking) VI - 13 IP - 4 DP - 1998 Oct TI - Antiproliferative action of tumor necrosis factor-alpha on MCF-7 breastcancer cells is associated with increased insulin-like growth factor binding protein-3 accumulation. PG - 865-9 AB - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine involved in host response to neoplasia. TNF-alpha has been shown to inhibit proliferation and induce apoptosis of MCF-7 breast carcinoma cells. Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens involved in growth regulation of breast epithelial cells and are implicated in the pathophysiology of breast cancer. Their bioactivity is strongly influenced by specific IGF-binding proteins (IGFBPs). We report that accumulation of IGFBP-3 in the conditioned media of MCF-7 cells is increased over control values in the presence of TNF-alpha. The increased IGFBP-3 accumulation induced by TNF-alpha is correlated with increased IGFBP-3 mRNA abundance. TNF-alpha also decreases IGF-I receptor levels in MCF-7 cells. Estradiol-stimulated MCF-7 cell proliferation is associated with reduced IGFBP-3 accumulation, and we show that TNF-alpha attenuation of estradiol-stimulated proliferation is associated with increased IGFBP-3 accumulation. Finally, we demonstrate that an IGFBP-3 antisense oligodeoxynucleotide antagonizes TNF-alpha-induced inhibition of cell proliferation and TNF-alpha-induced IGFBP-3 accumulation. These data strongly suggest that IGFBP-3 plays a role in modulation of breast cancer cell proliferation by TNF-alpha. FAU - Rozen, F AU - Rozen F AD - Lady Davis Research Institute of the Jewish General Hospital and Departments of Medicine and Oncology, McGill University, Montreal, Quebec, H3T 1E2, Canada. FAU - Zhang, J AU - Zhang J FAU - Pollak, M AU - Pollak M LA - eng PT - Journal Article PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (Antineoplastic Agents) RN - 0 (Insulin-Like Growth Factor Binding Protein 3) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 10028-17-8 (Tritium) RN - 4TI98Z838E (Estradiol) RN - VC2W18DGKR (Thymidine) SB - IM MH - Antineoplastic Agents/*pharmacology MH - Blotting, Northern MH - Breast Neoplasms/*metabolism/pathology MH - Cell Division/drug effects MH - Dose-Response Relationship, Drug MH - Estradiol/pharmacology MH - Gene Expression/drug effects MH - Humans MH - Insulin-Like Growth Factor Binding Protein 3/*drug effects/genetics/metabolism MH - RNA, Messenger/drug effects/metabolism MH - Thymidine/metabolism MH - Tritium MH - Tumor Cells, Cultured/cytology/drug effects/metabolism MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 1998/09/15 00:00 MHDA- 1998/09/15 00:01 CRDT- 1998/09/15 00:00 PHST- 1998/09/15 00:00 [pubmed] PHST- 1998/09/15 00:01 [medline] PHST- 1998/09/15 00:00 [entrez] AID - 10.3892/ijo.13.4.865 [doi] PST - ppublish SO - Int J Oncol. 1998 Oct;13(4):865-9. doi: 10.3892/ijo.13.4.865.