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Growth-inhibitory effect of adiponectin via adiponectin receptor 1 on human breast cancer cells through inhibition of S-phase entry without inducing apoptosis

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Abstract

Adiponectin is one of the most important adipocytokines secreted from adipose tissue. In addition to its effects on glucose and fatty acid metabolism, it has been reported that adiponectin has a direct growth-inhibitory effect on breast cancer cells. However, it still remains to be established how adiponectin affects cell cycle and apoptosis and whether or not its inhibitory effect is mediated through adiponectin receptors. Here, we demonstrated that adiponectin treatment resulted in a significant dose-dependent growth inhibition of both MDA-MB-231 and T47D cells. In both cell lines, the G0/G1 population significantly increased after adiponectin treatment, but apoptosis was not induced. High expression of mRNA and protein of adiponectin receptor 1 was observed, but expression of adiponectin receptor 2 was very low in both cell lines. Treatment with small interference RNA against adiponectin receptor 1 significantly reduced the growth inhibition induced by adiponectin in both cell lines. Taken together, adiponectin decreases breast cancer cell proliferation by inhibiting the entry into S-phase without inducing apoptosis, and this inhibitory effect is mediated through adiponectin receptor 1.

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Abbreviations

AdipoR1:

Adiponectin receptor 1

AdipoR2:

Adiponectin receptor 2

PBS:

Phosphate-buffered saline

SDS:

Sodium dodecyl sulfate

TBST:

Tris-buffered saline with Tween-20

TUNEL:

Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling

WST1:

Water-soluble tetrazolium

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Acknowledgments

This work was supported in part by a Grant-in-aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Correspondence to Shinzaburo Noguchi.

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Nakayama, S., Miyoshi, Y., Ishihara, H. et al. Growth-inhibitory effect of adiponectin via adiponectin receptor 1 on human breast cancer cells through inhibition of S-phase entry without inducing apoptosis. Breast Cancer Res Treat 112, 405–410 (2008). https://doi.org/10.1007/s10549-007-9874-3

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  • DOI: https://doi.org/10.1007/s10549-007-9874-3

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