Oestradiol treatment increases the sensitivity of MCF-7 cells for the growth stimulatory effect of IGF-I

Thorsen, T.; Lahooti, Hooshang; Rasmussen, Michael Højby; Aakvaag, A.

doi:10.1016/0960-0760(92)90379-w

Cited by 63 publications

(32 citation statements)

References 3 publications

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“…1A, stimulation of arrested cells with insulin (10 g/ml) or IGF-I (1 nM) alone resulted in a minor increase in S-phase cells to ϳ10 -12% at 26 h. Insulin dose-response experiments in serum-free medium without ICI 182780 indicated a maximal response between 100 ng/ml and 10 g/ml insulin (data not shown), and a similar maximal response was achieved with 1 nM IGF-I. A supraphysiological concentration (10 g/ml) of insulin, known to activate both insulin and IGF-I receptor signaling in breast epithelial cells (44,45), was used in all subsequent experiments, in agreement with the design of earlier studies demonstrating synergistic effects on breast epithelial cell proliferation (15,16,46). In marked contrast, estradiol (100 nM) alone stimulated a significantly greater S-phase entry of 43%.…”

Section: Synergistic Effects Of Estradiol and Insulin/igf-i On G 1 -Ssupporting

confidence: 49%

Insulin/Insulin-like Growth Factor-I and Estrogen Cooperate to Stimulate Cyclin E-Cdk2 Activation and Cell Cycle Progression in MCF-7 Breast Cancer Cells through Differential Regulation of Cyclin E and p21WAF1/Cip1

Lai

Šarčević

Prall

et al. 2001

Journal of Biological Chemistry

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Estrogens and insulin/insulin-like growth factor-I (IGF-I) are potent mitogens for breast epithelial cells and, when co-administered, induce synergistic stimulation of cell proliferation. To investigate the molecular basis of this effect, a MCF-7 breast cancer cell model was established where serum deprivation and concurrent treatment with the pure estrogen antagonist, ICI 182780, inhibited growth factor and estrogen action and arrested cells in G 0 /G 1 phase. Subsequent stimulation with insulin or IGF-I alone failed to induce significant Sphase entry. However, these treatments increased cyclin D1, cyclin E, and p21 gene expression and induced the formation of active Cdk4 complexes but resulted in only minor increases in cyclin E-Cdk2 activity, likely due to recruitment of the cyclin-dependent kinase (CDK) inhibitor p21 WAF1/Cip1 into these complexes. Treatment with estradiol alone resulted in a greater increase in cyclin D1 gene expression but markedly decreased p21 expression, with a concurrent increase in Cdk4 and Cdk2 activity and subsequent synchronous entry of cells into S phase. Co-administration of insulin/ IGF-I and estrogen induced synergistic stimulation of S-phase entry coincident with synergistic activation of high molecular mass (ϳ350 kDa) cyclin E-Cdk2 complexes lacking p21. To determine if the ability of estrogen to deplete p21 was central to these effects, cells stimulated with insulin and estradiol were infected with an adenovirus expressing p21. Induction of p21 to levels equivalent to those following treatment with insulin alone markedly inhibited the synergism between estradiol and insulin on S-phase entry. Thus the ability of estradiol to antagonize the insulin-induced increase in p21 gene expression, with consequent activation of cyclin E-Cdk2, is a central component of the synergistic stimulation of breast epithelial cell proliferation induced by simultaneous activation of the estrogen and insulin/IGF-I signaling pathways.

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Section: Synergistic Effects Of Estradiol and Insulin/igf-i On G 1 -Ssupporting

confidence: 49%

Insulin/Insulin-like Growth Factor-I and Estrogen Cooperate to Stimulate Cyclin E-Cdk2 Activation and Cell Cycle Progression in MCF-7 Breast Cancer Cells through Differential Regulation of Cyclin E and p21WAF1/Cip1

Lai

Šarčević

Prall

et al. 2001

Journal of Biological Chemistry

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“…The larger effects of IGF-1 in these earlier studies were most likely due to the low levels of residual E 2 in the culture medium or the presence of the phenol-red dye, a weak E 2 (Berthois et al, 1986). Hence, studies which used a more severe E 2 -withdrawal regimen lasting almost a week, as well as phenol-red free medium, observed very small effects of IGF-1 on MCF 7 cell proliferation (Stewart et al, 1990(Stewart et al, , 1992Thorsen et al, 1992;Wiseman et al, 1993). However, all of these studies were able to demonstrate a marked synergistic effect of E 2 and IGF-1 on MCF 7 cell proliferation despite the , E 2 (10 -9 M), tamoxifen (10 -6 M) and E 2 (10 -9 M) + tamoxifen (10 -6 M).…”

Section: Discussionmentioning

confidence: 99%

Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast cancer cell line

Parisot

Deluise

et al. 1999

Br J Cancer

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SummaryThe relationship between oestrogen (E 2 ) and insulin-like growth factor-one (IGF-1) was examined in both tamoxifen-sensitive (MCF 7/5-21) and tamoxifen-resistant (MCF 7/5-23) subclones of the MCF 7 cell line. Both subclones were grown in defined, serum-free (SF) medium over a period of 7 days with the addition of E 2 or IGF-1 or a combination of both agents. Growth of both MCF 7/5-21 and 7/5-23 cells was stimulated (245% and 350%, respectively) by E 2 . However, only the growth of MCF 7/5-23 cells was stimulated (266%) by IGF-1. A combination of E 2 and IGF-1 significantly enhanced MCF 7/5-21 and 7/5-23 cell growth (581% and 695%, respectively). E 2 -induced IGF-1 receptor (IGF-1R) levels (as measured by 125 I-IGF-1 binding and Northern analyses) in only MCF 7/5-23 cells. This effect was partially inhibited by tamoxifen. In medium containing serum, the growth of only the MCF 7/5-23 cells was significantly inhibited by the IGF-1R monoclonal antibody, αIR-3. The detection of E 2 -induced expression of IGF-2 using RT-PCR was demonstrated in the MCF 7/5-23 cells. These experiments indicate that E 2 may sensitize tamoxifen-resistant MCF 7/5-23 cells to the growth stimulatory actions of IGF-2 via upregulation of the IGF-1R and describes a cell-survival mechanism that may manifest itself as tamoxifen resistance.

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“…Synergism between IGF-1 and oestradiol has been con®rmed in stimulating the growth of human mammary cancer cell lines (Thorsen et al, 1992). Oestradiol may sensitise mammary cells to the proliferative effect of IGF-1 either by increasing IGF-1 receptor expression or by increasing cellular IGFBPs (McGuire et al, 1992).…”

Section: Insulin-like Growth Factor Activity and Breast Cancer Riskmentioning

confidence: 99%

Western nutrition and the insulin resistance syndrome: A link to breast cancer

1999

Eur J Clin Nutr

108

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Objective: The incidence of breast cancer in the Western world runs parallel to that of the major components of the insulin resistance syndrome Ð hyperinsulinaemia, dyslipidaemia, hypertension and atherosclerosis. Evidence is reviewed that the growth of breast cancer is favoured by speci®c dietary fatty acids, visceral fat accumulation and inadequate physical exercise, all of which are thought to interact in favouring the development of the insulin resistance syndrome. Design: Clinical, epidemiological and experimental studies linking breast cancer risk with evidence of insulin resistance and its concomitants, were searched for in the MEDLINE database since 1985. Results: Clinical and epidemiological evidence suggests that both breast cancer and the metabolic disorders comprising the insulin resistance syndrome are polygenic and multifactorial in origin. Experimental evidence suggests that hyperinsulinaemia and its concomitants can increase the promotion of mammary carcinogenesis and the mechanism is likely to involve increased bioactivity of insulin-like growth factor 1 (IGF-1). Case-control and cohort studies have shown that higher serum levels of IGF-1 are associated with increased breast cancer risk. Pharmacological agents which lower IGF-1 concentrations are under clinical trial for breast cancer prevention. Conclusions: Nutritional and lifestyle modi®cations that improve insulin sensitivity may not only decrease a tendency to atherosclerosis but also reduce breast cancer risk in women. In addition to a reduced fat intake, the dietary regimen might involve a reduced n-6/n-3 ratio of polyunsaturated fatty acids and should be associated with avoidance of obesity and regular physical exercise. Interventions to decrease breast cancer risk in ®rst-degree relatives of breast cancer patients need to begin at an early age.

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Oestradiol treatment increases the sensitivity of MCF-7 cells for the growth stimulatory effect of IGF-I

Cited by 63 publications

References 3 publications

Insulin/Insulin-like Growth Factor-I and Estrogen Cooperate to Stimulate Cyclin E-Cdk2 Activation and Cell Cycle Progression in MCF-7 Breast Cancer Cells through Differential Regulation of Cyclin E and p21WAF1/Cip1

Insulin/Insulin-like Growth Factor-I and Estrogen Cooperate to Stimulate Cyclin E-Cdk2 Activation and Cell Cycle Progression in MCF-7 Breast Cancer Cells through Differential Regulation of Cyclin E and p21WAF1/Cip1

Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast cancer cell line

Western nutrition and the insulin resistance syndrome: A link to breast cancer

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