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Effects of adiponectin on breast cancer cell growth and signaling.

Grossmann ME, Nkhata KJ, Mizuno NK, Ray A, Cleary MP - Br. J. Cancer (2008)

Bottom Line: In addition, we found that the addition of Acrp30 to MCF-7, T47D, and SK-BR-3 cell lines inhibited growth.In vitro, MDA-ERalpha7 cells were growth inhibited by globular Acrp30 while the parental cells were not.This inhibition appeared to be due to blockage of JNK2 signalling.

View Article: PubMed Central - PubMed

Affiliation: Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.

ABSTRACT
Obesity is a risk factor for postmenopausal breast cancer. Adiponectin/Acrp30 is lower in obese individuals and may be negatively regulating breast cancer growth. Here we determined that five breast cancer cell lines, MDA-MB-231, MDA-MB-361, MCF-7, T47D, and SK-BR-3, expressed one or both of the Acrp30 receptors. In addition, we found that the addition of Acrp30 to MCF-7, T47D, and SK-BR-3 cell lines inhibited growth. Oestrogen receptor (ER) positive MCF-7 and T47D cells were inhibited at lower Acrp30 concentrations than ER-negative SK-BR-3 cells. Growth inhibition may be related to apoptosis since PARP cleavage was increased by Acrp30 in the ER-positive cell lines. To investigate the role of ER in the response of breast cancer cells to Acrp30, we established the MDA-ERalpha7 cell line by insertion of ER-alpha into ER-alpha-negative MDA-MB-231 cells. This line readily formed tumours in athymic mice and was responsive to oestradiol in vivo. In vitro, MDA-ERalpha7 cells were growth inhibited by globular Acrp30 while the parental cells were not. This inhibition appeared to be due to blockage of JNK2 signalling. These results provide information on how obesity may influence breast cancer cell proliferation and establish a new model to examine interactions between ER and Acrp30.

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Growth of MDA-wt and clones expressing ERα in response to oestradiol in vivo. Rag1 mice were injected with the cell lines shown along the x axis in the presence (E) or absence (C) of oestradiol pellets. Mice were intact for experiment 1 and ovariectomised in experiment 2. Tumours were excised, weighed and measured at the end of the experiment. The average volume in millimetres of the tumours are shown in (A) and (C) and the average weight in milligrams are shown in (B) and (D) along the y axis for experiments one and two respectively. The. volume for each individual tumour was computed according to the formula length ((longest dimension) × width squared (widest point at right angle to length) × 0.52). The different groups are shown along the x axis. Bars represent standard error of the mean. An ‘a' above the bars shows groups that are statically different than all other groups as determined by ANOVA with Newman–Keul's multiple comparison post-test (P<0.01).
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fig3: Growth of MDA-wt and clones expressing ERα in response to oestradiol in vivo. Rag1 mice were injected with the cell lines shown along the x axis in the presence (E) or absence (C) of oestradiol pellets. Mice were intact for experiment 1 and ovariectomised in experiment 2. Tumours were excised, weighed and measured at the end of the experiment. The average volume in millimetres of the tumours are shown in (A) and (C) and the average weight in milligrams are shown in (B) and (D) along the y axis for experiments one and two respectively. The. volume for each individual tumour was computed according to the formula length ((longest dimension) × width squared (widest point at right angle to length) × 0.52). The different groups are shown along the x axis. Bars represent standard error of the mean. An ‘a' above the bars shows groups that are statically different than all other groups as determined by ANOVA with Newman–Keul's multiple comparison post-test (P<0.01).

Mentions: We felt that the most relevant way to determine if the addition of ERα is providing a growth advantage for the MDA-ERα clones was to perform in vivo experiments. Therefore, we injected the MDA-ERα5, MDA-ERα7, and MDA-wt cells into athymic Rag1 C57BL/6 female mice using oestradiol or placebo pellets in the mice implanted with the MDA-ERα clones. The MDA-ERα7 cells in mice with exogenous oestrogen formed heavier tumours (Figure 3A) compared to the other groups (164 vs 24–81 mg) and grew to a considerably larger size (Figure 3B) compared to any of the other experimental groups (172 vs 41–103 mm3) (ANOVA P<0.01 with Newman–Keul's multiple comparison test P<0.01 or more for all groups). The MDA-wt grew slowest although this was not statistically significant compared to any of the other groups except for the MDA-ERα7 with exogenous oestrogen. The tumours in the groups inoculated with MDA-ERα5 cells in the presence or absence of exogenous oestradiol and the MDA-ERα7 cells in the absence of exogenous oestradiol all grew at almost the same rate.


Effects of adiponectin on breast cancer cell growth and signaling.

Grossmann ME, Nkhata KJ, Mizuno NK, Ray A, Cleary MP - Br. J. Cancer (2008)

Growth of MDA-wt and clones expressing ERα in response to oestradiol in vivo. Rag1 mice were injected with the cell lines shown along the x axis in the presence (E) or absence (C) of oestradiol pellets. Mice were intact for experiment 1 and ovariectomised in experiment 2. Tumours were excised, weighed and measured at the end of the experiment. The average volume in millimetres of the tumours are shown in (A) and (C) and the average weight in milligrams are shown in (B) and (D) along the y axis for experiments one and two respectively. The. volume for each individual tumour was computed according to the formula length ((longest dimension) × width squared (widest point at right angle to length) × 0.52). The different groups are shown along the x axis. Bars represent standard error of the mean. An ‘a' above the bars shows groups that are statically different than all other groups as determined by ANOVA with Newman–Keul's multiple comparison post-test (P<0.01).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2361440&req=5

fig3: Growth of MDA-wt and clones expressing ERα in response to oestradiol in vivo. Rag1 mice were injected with the cell lines shown along the x axis in the presence (E) or absence (C) of oestradiol pellets. Mice were intact for experiment 1 and ovariectomised in experiment 2. Tumours were excised, weighed and measured at the end of the experiment. The average volume in millimetres of the tumours are shown in (A) and (C) and the average weight in milligrams are shown in (B) and (D) along the y axis for experiments one and two respectively. The. volume for each individual tumour was computed according to the formula length ((longest dimension) × width squared (widest point at right angle to length) × 0.52). The different groups are shown along the x axis. Bars represent standard error of the mean. An ‘a' above the bars shows groups that are statically different than all other groups as determined by ANOVA with Newman–Keul's multiple comparison post-test (P<0.01).
Mentions: We felt that the most relevant way to determine if the addition of ERα is providing a growth advantage for the MDA-ERα clones was to perform in vivo experiments. Therefore, we injected the MDA-ERα5, MDA-ERα7, and MDA-wt cells into athymic Rag1 C57BL/6 female mice using oestradiol or placebo pellets in the mice implanted with the MDA-ERα clones. The MDA-ERα7 cells in mice with exogenous oestrogen formed heavier tumours (Figure 3A) compared to the other groups (164 vs 24–81 mg) and grew to a considerably larger size (Figure 3B) compared to any of the other experimental groups (172 vs 41–103 mm3) (ANOVA P<0.01 with Newman–Keul's multiple comparison test P<0.01 or more for all groups). The MDA-wt grew slowest although this was not statistically significant compared to any of the other groups except for the MDA-ERα7 with exogenous oestrogen. The tumours in the groups inoculated with MDA-ERα5 cells in the presence or absence of exogenous oestradiol and the MDA-ERα7 cells in the absence of exogenous oestradiol all grew at almost the same rate.

Bottom Line: In addition, we found that the addition of Acrp30 to MCF-7, T47D, and SK-BR-3 cell lines inhibited growth.In vitro, MDA-ERalpha7 cells were growth inhibited by globular Acrp30 while the parental cells were not.This inhibition appeared to be due to blockage of JNK2 signalling.

View Article: PubMed Central - PubMed

Affiliation: Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.

ABSTRACT
Obesity is a risk factor for postmenopausal breast cancer. Adiponectin/Acrp30 is lower in obese individuals and may be negatively regulating breast cancer growth. Here we determined that five breast cancer cell lines, MDA-MB-231, MDA-MB-361, MCF-7, T47D, and SK-BR-3, expressed one or both of the Acrp30 receptors. In addition, we found that the addition of Acrp30 to MCF-7, T47D, and SK-BR-3 cell lines inhibited growth. Oestrogen receptor (ER) positive MCF-7 and T47D cells were inhibited at lower Acrp30 concentrations than ER-negative SK-BR-3 cells. Growth inhibition may be related to apoptosis since PARP cleavage was increased by Acrp30 in the ER-positive cell lines. To investigate the role of ER in the response of breast cancer cells to Acrp30, we established the MDA-ERalpha7 cell line by insertion of ER-alpha into ER-alpha-negative MDA-MB-231 cells. This line readily formed tumours in athymic mice and was responsive to oestradiol in vivo. In vitro, MDA-ERalpha7 cells were growth inhibited by globular Acrp30 while the parental cells were not. This inhibition appeared to be due to blockage of JNK2 signalling. These results provide information on how obesity may influence breast cancer cell proliferation and establish a new model to examine interactions between ER and Acrp30.

Show MeSH
Related in: MedlinePlus