American Association for Cancer Research
15357163mct110545-sup-sdata_6_pdf_119k.pdf (119.09 kB)

Supplementary Data 6 from Direct Role of Adiponectin and Adiponectin Receptors in Endometrial Cancer: In Vitro and Ex Vivo Studies in Humans

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journal contribution
posted on 2023-04-03, 13:24 authored by Hyun-Seuk Moon, John P. Chamberland, Konstantinos Aronis, Sofia Tseleni-Balafouta, Christos S. Mantzoros

PDF file - 119K, The cell culture and introduction of LKB1 siRNA were performed as described in detail in the "Methods" section. The cells were treated with adiponectin (20 �g/ml) for 24hr. C: Control; ssi: scrambled siRNA; si: LKB1 siRNA. All density values for each graph of interest are expressed as fold increases. All data were analyzed using one-way ANOVA followed by post-hoc test for multiple comparisons. Values are means (n=3) � SD. Means with different letters are significantly different, p<0.05.



Low adiponectin levels are an independent risk factor for and mediate the effect of obesity on endometrial cancer in epidemiology studies. The direct or indirect mechanisms underlying these findings remain to be elucidated. We first examined the expression of adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) in normal human endometrium and in endometrial cancer tissues ex vivo. We then used KLE and RL95-2 human endometrial cancer cell lines in vitro to study relative expression of AdipoRs, to investigate the effect of adiponectin on activating intracellular signaling pathways, and to assess its potential to alter malignant properties. We report for the first time that the relative expression level of AdipoR1 is higher than AdipoR2 in human endometrial cancer tissue, but the expression of AdipoRs is not statistically different from nonneoplastic tissues. We also show for the first time in endometrial cancer cell lines in vitro that adiponectin suppresses endometrial cancer proliferation acting through AdipoRs. Adiponectin also increases the expression of the adaptor molecule LKB1, which is required for adiponectin-mediated activation of AMPK/S6 axis and modulation of cell proliferation, colony formation, adhesion, and invasion of KLE and RL95-2 cell lines. These novel mechanistic studies provide for the first time in vitro and ex vivo evidence for a causal role of adiponectin in endometrial cancer. Mol Cancer Ther; 10(12); 2234–43. ©2011 AACR.