The control of progesterone receptor expression in MCF-7 breast cancer cells: effects of estradiol and sex hormone-binding globulin (SHBG)

Fazzari, Annamaria; Catalano, Maria Graziella; Comba, Alessandra; Becchis, Marzia; Raineri, Mariangela; Frairia, Roberto; Fortunati, Nicoletta

doi:10.1016/s0303-7207(00)00397-x

Cited by 40 publications

(30 citation statements)

References 19 publications

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“…This effect could also be linked to apoptosis induction and cell growth inhibition, since, as reported by other authors [37,38] , both phenomena were observed when ER expression was increased in association with bcl-2 reduction. As PR modulation is concerned, SHBG completely inhibits the strong upregulation induced by estradiol both at mRNA and protein levels as previously reported [17] ; data reported in the present paper, obtained from gene array, further confi rm our previous observation. The selectivity of SHBG effect on gene expression confi rms that SHBG regulation of estradiol effect in MCF-7 cells is not a general effect, due to the steroid sequester.…”

Section: Discussionsupporting

confidence: 92%

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Sex Hormone-binding Globulin Selectively Modulates Estradiol-regulated Genes in MCF-7 Cells

Catalano¹,

Costantino²,

Frairia³

et al. 2007

Horm Metab Res

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&Human sex hormone-binding globulin inhibits the effects of estradiol on proliferation and apoptosis of breast cancer cells. We report here the effect of sex hormone-binding globulin on estradiol regulation of gene expression in MCF-7 breast cancer cells using a selected set of genes. Estradiol upregulates genes that are positive regulators of proliferation (e.g., bcl-2, c-fos, cmyc, cyclin D) or / and related to more aggressive form of breast cancer (e.g. BRCA-1, EGF-R) and downregulates two genes (c-jun and ER ).Sex hormone-binding globulin modulates only a selected group of estradiol-controlled genes (inhibiting upregulation of bcl-2, c-myc, EGF-R, PR, and downregulation of ER ), starting 48 hours after treatment. Our study demonstrates that in breast cancer cells, sex hormone-binding globulin is effective on few selected genes which are involved in cell growth and apoptosis or related to cell estrogen-dependence and that the protein regulation of estradiol effect is selected and specifi c. Sex hormone-binding globulin action in estrogen breast cancer cells is strongly associated to cell growth and estrogen-sensitivity.

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Section: Discussionsupporting

confidence: 92%

“…As progesterone receptor is concerned, we confi rmed our previously results [17] indicating that estradiol induces PR expression and that pretreatment with SHBG determine a reduction of PR to basal levels, again at both mRNA and protein levels.…”

Section: Shbg Regulation Of Steroid Receptor Expression (Er and Pr)supporting

confidence: 85%

Sex Hormone-binding Globulin Selectively Modulates Estradiol-regulated Genes in MCF-7 Cells

Catalano¹,

Costantino²,

Frairia³

et al. 2007

Horm Metab Res

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show abstract

“…A recent study demonstrated that, either in ER+ or ER-cell context, progestins induced proliferation and regulated proteases activity and metastasis through PR ability to activate c-Src dependent signaling pathways (28). The expression of PR is up-regulated by estrogen stimulation (29), hence PR expression might be affected by exercise via reduced estrogen levels. Further, there is some limited evidence, that exercise may decrease plasma levels of progesterone (30,31).…”

Section: Discussionmentioning

confidence: 99%

Physical Activity and Postmenopausal Breast Cancer: Effect Modification by Breast Cancer Subtypes and Effective Periods in Life

Schmidt

Steindorf

Mutschelknauss

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Physical activity (PA) has been inversely associated with postmenopausal breast cancer risk. However, it is unclear how and in which life periods PA may be effective to reduce breast cancer risk. Moreover, the evidence is still not judged as 'convincing' as there is some heterogeneity among study results. Most studies regarded breast cancer as a single disease, at best separated by menopausal status. Yet, breast cancers are heterogeneous and likely have different etiologies. Therefore, we analyzed the association of PA with different breast cancer subtypes in 3,414 postmenopausal cases and 6,569 controls from a case-control study on breast cancer conducted [2002][2003][2004][2005] in Germany (MARIE study). PA in the age periods 30-49 and 50+ years was assessed, including leisure-time PA (sports, cycling, walking) and non-recreational PA (occupational and household activities). There was a significant protective effect of leisure-time PA for ER+/PR+ carcinomas (adjusted odds ratio = 0.71, 95% confidence interval: 0.60, 0.85; trend P = 0.0001), but no effect for ER-/PRcarcinomas. Moreover, looking at physical activity pattern over time, the effect of PA after menopause on reducing breast cancer risk was more pronounced than the effect of PA before menopause. Overall, effects of PA were independent from adult weight gain, body mass index, and energy intake. These findings suggest that leisure-time PA after menopause may reduce postmenopausal breast cancer risk at least in part via hormonal pathways and not solely by changing body composition. Inactive postmenopausal women should be encouraged to become physically active even later in life. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3402 -10)

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“…In breast cancer cells, SHBG, through its specific membrane receptor (SHBG-R) and second messenger system (cyclic AMP and protein kinase A), not only effectively inhibits estradiolinduced cell proliferation but also controls progesterone receptor expression at both the mRNA and protein levels, and influences its function (receptor binding capacity; refs. 5,6). A number of epidemiologic studies have shown that blood SHBG levels are inversely associated with breast cancer risk (7,8).…”

Section: Introductionmentioning

confidence: 99%

Association of Breast Cancer Risk with a Common Functional Polymorphism (Asp327Asn) in the Sex Hormone–Binding Globulin Gene

Cui

Shu

Cai

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Sex hormones play a central role in the development of breast cancer. Sex hormone -binding globulin (SHBG) modulates the bioavailability of circulating sex hormones and regulates their signaling system in the breast tissue. We evaluated the association of a common functional polymorphism (Asp327Asn) in the SHBG gene with breast cancer risk in a population-based case-control study (1,106 cases and 1,180 controls) conducted in Shanghai, China. The variant Asn allele was associated with a reduced breast cancer risk in postmenopausal women [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.53-0.99], but not in premenopausal women (OR, 1.03; 95% CI, 0.82-1.27). The protective association was much stronger in postmenopausal women with a low body mass index (BMI; OR, 0.46; 95% CI, 0.29-0.75) or waist-to-hip ratio (OR, 0.51; 95% CI, 0.32-0.83) than those with a high BMI or waist-to-hip ratio (P for interaction < 0.05). Furthermore, the association was stronger for estrogen receptor -positive (OR, 0.64; 95% CI, 0.42-0.98) than for estrogen receptor -negative breast cancer (OR, 0.85; 95% CI, 0.50-1.45). Among postmenopausal controls, blood SHBG levels were 10% higher in carriers of the variant Asn allele than noncarriers (P = 0.06). Postmenopausal control women with the Asn allele and low BMI or waist-to-hip ratio had 20% higher SHBG levels (P < 0.05). This study suggests that the Asn allele in the SHBG gene may be related to a reduced risk of breast cancer among postmenopausal women by increasing their blood SHBG levels. (Cancer Epidemiol

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The control of progesterone receptor expression in MCF-7 breast cancer cells: effects of estradiol and sex hormone-binding globulin (SHBG)

Cited by 40 publications

References 19 publications

Sex Hormone-binding Globulin Selectively Modulates Estradiol-regulated Genes in MCF-7 Cells

Sex Hormone-binding Globulin Selectively Modulates Estradiol-regulated Genes in MCF-7 Cells

Physical Activity and Postmenopausal Breast Cancer: Effect Modification by Breast Cancer Subtypes and Effective Periods in Life

Association of Breast Cancer Risk with a Common Functional Polymorphism (Asp327Asn) in the Sex Hormone–Binding Globulin Gene

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