Antiproliferative action of tumor necrosis factor-alpha on MCF-7 breastcancer cells is associated with increased insulin-like growth factor binding protein-3 accumulation
Autor: | Michael Pollak, Florence Rozen, Jianchun Zhang |
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Rok vydání: | 1998 |
Předmět: |
Cancer Research
medicine.medical_specialty medicine.medical_treatment Cell Gene Expression Antineoplastic Agents Breast Neoplasms Biology Tritium Internal medicine medicine Tumor Cells Cultured Humans RNA Messenger Oncogene Dose-Response Relationship Drug Estradiol Cell growth Tumor Necrosis Factor-alpha Cell cycle Blotting Northern Endocrinology medicine.anatomical_structure Cytokine Insulin-Like Growth Factor Binding Protein 3 Oncology MCF-7 Cell culture Cancer research Tumor necrosis factor alpha hormones hormone substitutes and hormone antagonists Cell Division Thymidine |
Zdroj: | International journal of oncology. 13(4) |
ISSN: | 1019-6439 |
Popis: | 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. |
Databáze: | OpenAIRE |
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