scholarly journals Role of Insulin-Like Growth Factor Binding Protein-3 in 1, 25-Dihydroxyvitamin-D3-Induced Breast Cancer Cell Apoptosis

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
C. Brosseau ◽  
G. Pirianov ◽  
K. W. Colston
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Igf I ◽  
Induced Apoptosis ◽  
Parp 1 ◽  
Mcf 7 ◽  
Igfbp 3

Insulin-like growth factor I (IGF-I) is implicated in breast cancer development and 1, 25-dihydroxyvitamin D3(1, 25-D3) has been shown to attenuate prosurvival effects of IGF-I on breast cancer cells. In this study the role of IGF binding protein-3 (IGFBP-3) in 1, 25-D3-induced apoptosis was investigated using parental MCF-7 breast cancer cells and MCF-7/VDRcells, which are resistant to the growth inhibitory effects of 1, 25-D3. Treatment with 1, 25-D3increased IGFBP-3 mRNA expression in both cell lines but increases in intracellular IGFBP-3 protein and its secretion were observed only in MCF-7. 1, 25-D3-induced apoptosis was not associated with activation of any caspase but PARP-1 cleavage was detected in parental cells. IGFBP-3 treatment alone produced cleavage of caspases 7, 8, and 9 and PARP-1 in MCF-7 cells. IGFBP-3 failed to activate caspases in MCF-7/VDRcells; however PARP-1 cleavage was detected. 1, 25-D3treatment inhibited IGF-I/Akt survival signalling in MCF-7 but not in MCF-7/VDRcells. In contrast, IGFBP-3 treatment was effective in inhibiting IGF-I/Akt pathways in both breast cancer lines. These results suggest a role for IGFBP-3 in 1, 25-D3apoptotic signalling and that impaired secretion of IGFBP-3 may be involved in acquired resistance to vitamin D in breast cancer.

Role of specific apoptotic pathways in the restoration of paclitaxel-induced apoptosis by valspodar in doxorubicin-resistant MCF-7 breast cancer cells

2000 ◽  
Vol 59 (3) ◽  
pp. 231-244 ◽  
Author(s):  
Antony Chadderton ◽  
David J. Villeneuve ◽  
Stefan Gluck ◽  
Angie F. Kirwan-Rhude ◽  
Brian R. Gannon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Apoptotic Pathways ◽  
Induced Apoptosis ◽  
Mcf 7

INSULIN-LIKE GROWTH FACTOR TYPE I AND INSULIN-LIKE GROWTH FACTOR TYPE II STIMULATE OESTRADIOL-17β HYDROXYSTEROID DEHYDROGENASE (REDUCTIVE) ACTIVITY IN BREAST CANCER CELLS

1991 ◽  
Vol 129 (2) ◽  
pp. R5-R8 ◽  
Author(s):  
Anita Singh ◽  
M.J. Reed
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Hydroxysteroid Dehydrogenase ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Factor Type ◽  
Mcf 7

ABSTRACT Oestradiol-17β hydroxysteroid dehydrogenase (E2DH) is present in normal and malignant breast tissues and also in cultured breast cancer cells. It can act in a reductive direction to convert oestrone to the biologically active oestrogen, oestradiol, or in an oxidative direction to metabolize oestradiol to oestrone and may therefore have a crucial role in regulating breast tissue concentrations of oestradiol. Insulin-like growth factor-type I (IGF-I) and IGF-II are both mitogens for breast cancer cells. In this study we have examined the effect of these growth factors on the reductive and oxidative activities of E2DH in MCF-7 (receptor positive) and MDA-MB-231 (receptor negative) breast cancer cells. Both IGF-I (80 ng/ml) and IGF-II (80 ng/ml) significantly stimulated E2DH reductive activity (up to 138%) in MCF-7 cells but had no effect on oxidative activity. Addition of IGF-II (100 ng/ml) to MDA-MB-231 cells resulted in a small but statistically significant (p<0.05) increase in E2DH reductive activity (18%) but in these cells reductive activity is 25-70 times lower than oxidative activity. If IGF-I and IGF-II act to stimulate E2DH reductive activity in breast tumours then such a mechanism could account for the increased concentrations of oestradiol detected in breast tumours.

scholarly journals Role of estrogen receptor (ER) α in insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells

2005 ◽  
Vol 35 (3) ◽  
pp. 433-447 ◽  
Author(s):  
S Zhang ◽  
X Li ◽  
R Burghardt ◽  
R Smith ◽  
S H Safe
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Growth Factor ◽  
Breast Cancer Cells ◽  
S Phase ◽  
Induced Responses ◽  
Igf I ◽  
Phase Progression ◽  
Mcf 7

Insulin-like growth factor-I (IGF-I) is a mitogenic polypeptide that induces proliferation of MCF-7 breast cancer cells, and cotreatment with the phosphoinositide 3-kinase (PI3-K) inhibitor LY294002 and the antiestrogen ICI 182780 inhibits IGF-I-induced growth. The role of estrogen receptor α (ERα) in mediating responses induced by IGF-I was investigated in cells transfected with small inhibitory RNA for ERα (iERα). The results showed that IGF-I-dependent phosphorylation of Akt and mitogen-activated protein kinase, induction of G1–S-phase progression and enhanced expression of cyclin D1 and cyclin E were dependent on ERα. Moreover, these same IGF-I-induced responses were also inhibited by the antiestrogen ICI 182780 and this was in contrast to a previous report suggesting that ICI 182780 did not affect IGF-I-dependent activation of PI3-K or induction of cyclin D1 expression. ICI 182780 exhibits antimitogenic activity and iERα inhibits G1–S-phase progression and proliferation of MCF-7 cells treated with IGF-I, suggesting that the effects of the antiestrogen are primarily related to downregulation of ERα.

scholarly journals Estrogen Signaling via a Linear Pathway Involving Insulin-Like Growth Factor I Receptor, Matrix Metalloproteinases, and Epidermal Growth Factor Receptor to Activate Mitogen-Activated Protein Kinase in MCF-7 Breast Cancer Cells

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 4091-4101 ◽  
Author(s):  
Robert X.-D. Song ◽  
Zhenguo Zhang ◽  
Yucai Chen ◽  
Yongde Bao ◽  
Richard J. Santen
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mapk Activation ◽  
Igf I ◽  
Sequential Activation ◽  
Epidermal Growth ◽  
Mcf 7

We present an integrated model of an extranuclear, estrogen receptor-α (ERα)-mediated, rapid MAPK activation pathway in breast cancer cells. In noncancer cells, IGF-I initiates a linear process involving activation of the IGF-I receptor (IGF-IR) and matrix metalloproteinases (MMP), release of heparin-binding epidermal growth factor (HB-EGF), and activation of EGF receptor (EGFR)-dependent MAPK. 17β-Estradiol (E2) rapidly activates IGF-IR in breast cancer cells. We hypothesize that E2 induces a similar linear pathway involving IGF-IR, MMP, HB-EGF, EGFR, and MAPK. Using MCF-7 breast cancer cells, we for the first time demonstrated that a sequential activation of IGF-IR, MMP, and EGFR existed in E2 and IGF-I actions, which was supported by evidence that the selective inhibitors of IGF-IR and MMP or knockdown of IGF-IR all inhibited E2- or IGF-I-induced EGFR phosphorylation. Using the inhibitors and small inhibitory RNA strategies, we also demonstrated that the same sequential activation of the receptors occurred in E2-, IGF-I-, but not EGF-induced MAPK phosphorylation. Additionally, a HB-EGF neutralizing antibody significantly blocked E2-induced MAPK activation, further supporting our hypothesis. The biological effects of sequential activation of IGF-IR and EGFR on E2 stimulation of cell proliferation were also investigated. Knockdown or blockade of IGF-IR significantly inhibited E2- or IGF-I-stimulated but not EGF-induced cell growth. Knockdown or blockade of EGFR abrogated cell growth induced by E2, IGF-I, and EGF, indicating that EGFR is a downstream molecule of IGF-IR in E2 and IGF-I action. Together, our data support the novel view that E2 can activate a linear pathway involving the sequential activation of IGF-IR, MMP, HB-EGF, EGFR, and MAPK.

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