Effects of adiponectin on breast cancer cell growth and signaling

Großmann, Matthias; Nkhata, Katai J.; Mizuno, Nancy K.; Ray, A.; Cleary, Margot P.

doi:10.1038/sj.bjc.6604166

Cited by 185 publications

(167 citation statements)

References 52 publications

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“…The serum levels of gAcrp30 in women with Brca have not yet been fully investigated, nor has the role of gAcrp30 in Brca development. We performed proliferation assays with the MDA-MB-231 (MDA-wt) ERα negative Brca cell line and the MDA-ERα7 cell line which we developed by stably integrating the ERα gene such that it now exhibits increased growth in vivo in the presence of exogenous estradiol [8]. Leptin is present in the serum of almost all humans in the range of 5-50 ng/ ml [9].…”

Section: Dear Editormentioning

confidence: 99%

Balance of adiponectin and leptin modulates breast cancer cell growth

et al. 2008

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There is lack of information concerning how the ratio of adiponectin to leptin in serum affects breast cancer (Brca) proliferation. It is possible that the link between obesity and increased risk for aggressive Brca is in part due to the milieu of cytokines synthesized and released by the adipose tissue [1]. Adiponectin (also known as adipocyte complement-related protein of 30 kDa (Acrp30)) and leptin are two specific cytokines secreted by the adipose tissue. Acrp30 serum levels decrease with increasing fatness while leptin levels increase. Functionally, they appear to oppose each other's actions. Acrp30 can block proliferation of Brca cells [2]. In vitro assays have shown that a number of different Brca cell lines express one or both of the Acrp30 receptors and show reduced growth and/or increased apoptosis in response to Acrp30 [3]. Leptin has been implicated as a growth-promoting factor for Brca [1]. Animal studies also support a role for leptin in mammary tumor development as evidenced by the fact that mice deficient in leptin, Lep ob Lep ob [4], or with non-functioning leptin receptors, Lepr db Lepr db [5], did not develop transgene-induced mammary tumors. It is possible that the levels of adiponectin and leptin receptors, as well as the balance of serum adiponectin and leptin, are critical factors in mammary tumorigenesis.We investigated the effects of Acrp30 and a naturally truncated form known as globular Acrp30 [6] (gAcrp30) in the presence or absence of leptin. There are two different Acrp30 receptors, designated as AdipoR1 and AdipoR2 [7]. Full-length Acrp30 binds with highest affinity to AdipoR2, and gAcrp30 binds with highest affinity to AdipoR1 [7]. The serum levels of gAcrp30 in women with Brca have not yet been fully investigated, nor has the role of gAcrp30 in Brca development. We performed proliferation assays with the MDA-MB-231 (MDA-wt) ERα negative Brca cell line and the MDA-ERα7 cell line which we developed by stably integrating the ERα gene such that it now exhibits increased growth in vivo in the presence of exogenous estradiol [8]. Leptin is present in the serum of almost all humans in the range of 5-50 ng/ ml [9]. However, in obese individuals levels in excess of 100 ng/ml are common. The addition of leptin (50 ng/ml) to these two cell lines caused a slight increase in proliferation ( Figure 1A) for both the MDA-wt and MDA-ERα7 cells after 48 h. Acrp30 is measured in human serum in the range of 2-20 μg/ml and is negatively correlated with body weight, BMI, body fat and serum leptin in women [10]. When these two cell lines were treated with Acrp30 and gAcrp30 there was a reduction in proliferation of the MDA-wt and MDA-ERα7 cells as compared to leptintreated cells. To investigate how changes in the ratio of leptin and Acrp30 or gAcrp30 affect cell growth, we performed proliferation assays using ratios of Acrp30 to leptin that simulate the physiological balance found with increasing body weight, i.e., by decreasing adiponectin and increasing leptin. A high ratio of Acrp30 to leptin caused...

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Section: Dear Editormentioning

confidence: 99%

Balance of adiponectin and leptin modulates breast cancer cell growth

et al. 2008

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“…In 2008, Grossmann ME and colleagues revealed that estrogen receptor positive MCF-7 and T47D cells were inhibited at lower adiponectin concentrations than ER-negative SK-BR-3 cells (Grossmann et al,2008). Miyoshi et al, Chen DC et al and Tworoger et al did not find an association between adiponectin levels and estrogen receptor status in their trials.…”

Section: Discussionmentioning

confidence: 92%

“…In breast cancer it is likely that obesity is often related to estrogen reseptor status (Kang et al, 2007;Grossmann et al, 2008;Karaduman et al, 2007). In 2008, Grossmann ME and colleagues revealed that estrogen receptor positive MCF-7 and T47D cells were inhibited at lower adiponectin concentrations than ER-negative SK-BR-3 cells (Grossmann et al,2008).…”

Section: Discussionmentioning

confidence: 99%

Associations between Adiponectin and Two Different Cancers: Breast and Colon

Gülçelik¹,

Colakoglu²,

Dincer³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Objectives: Breast and colon cancer are neoplasms well known to be related to obesity. Adiponectin, a protein that increases in obesity, seems to be involved in the relationship but clinical data are limited. Methods: In this study, we therefore evaluated the serum adiponectin levels in 87 breast and 27 colon cancer patients and assessed the relation with BMI, menopausal status, receptor status and stage of disease. Results: Serum adiponectin levels were lower in cancer cases (8583 ± 2095 ng/ml for breast cancer, 9513 ± 2276 for colon cancer) than in controls (13905 ± 3263). Conclusion: A low serum adiponectin level may be associated with both breast and colon cancer, and that this association is not statistically significant for either receptor or menopausal status in breast cancer groups.

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“…2007; Grossmann et al. 2008). This is mediated by ADIPO binding to its receptor Adiponectin receptor 1 (AdpoR1) which is also implicated in breast cancer (Dieudonne et al.…”

Section: Introductionmentioning

confidence: 99%

“…ADIPO‐dependent anti‐proliferative effects are abolished by siRNA knockdown of AdipoR1 (Grossmann et al. 2008; Nakayama et al. 2008).…”

Section: Introductionmentioning

confidence: 99%

Voluntary physical activity counteracts the proliferative tumor growth microenvironment created by adipose tissue via high-fat diet feeding in female rats

Theriau

Connor

2017

Physiol Rep

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The adipokine secretion profile created from adipose tissue may represent the molecular mechanism behind the obesity‐breast cancer association. Two adipokines, adiponectin (ADIPO), and leptin (LEP), are altered with obesity and exert antagonistic effects on breast cancer proliferation. We set out to determine whether the adipose‐dependent tumor promoting growth environment created by a high‐fat diet (HFD) in female Sprague‐Dawley rats is altered compared to established responses in male rats and whether voluntary physical activity (PA) ameliorates any HFD‐dependent effects. We found that conditioned media (CM) created from the adipose tissue of female HFD‐fed rats increased the proliferation of MCF7 cells compared to those cells grown in CM prepared from lean adipose tissue. HFD‐CM inhibited AMPK and activated Akt signaling, decreased p27 phosphorylation at T198, reduced total p27 and AdiporR1 protein levels and promoted cell‐cycle entry. PA reversed the proliferative effects of HFD‐CM on MCF7 cells by preventing the effects of HFD on AMPK, Akt, p27 and AdipoR1, ultimately resulting in cell‐cycle withdrawal. Overexpressing AdipoR1 abolished the proliferative effects of the HFD‐CM on MCF7 cells and enhanced the anti‐proliferative effects PA on the HFD‐CM. Thus, PA represents a means to prevent deleterious obesity‐related alterations in tumor growth environment which are brought about by changes in adipokine secretion profile from adipose tissue in the presence of estrogen. Furthermore, although adipose produces hundreds of adipokines, the ADIPO:LEP ratio may serve to indicate the contribution of adipose in creating a tumor growth microenvironment.

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Effects of adiponectin on breast cancer cell growth and signaling

Cited by 185 publications

References 52 publications

Balance of adiponectin and leptin modulates breast cancer cell growth

Balance of adiponectin and leptin modulates breast cancer cell growth

Associations between Adiponectin and Two Different Cancers: Breast and Colon

Voluntary physical activity counteracts the proliferative tumor growth microenvironment created by adipose tissue via high-fat diet feeding in female rats

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