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The pMAPK/pAMPK ratio modulates the effect of adiponectin on breast cancer cell growth
Author(s) -
Mauro Loredana,
Pellegrino Michele,
Ricchio Emilia,
De Amicis Francesca,
Catalano Stefania,
Bonofiglio Daniela,
Rizza Pietro,
Panno Maria Luisa,
Ando' Sebastiano
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1088.3
Subject(s) - adiponectin , endocrinology , adipose tissue , medicine , cancer research , cell growth , ampk , mapk/erk pathway , breast cancer , chemistry , cancer , phosphorylation , biology , microbiology and biotechnology , insulin , insulin resistance , protein kinase a , biochemistry
Adiponectin, an adipose tissue‐derived hormone, may influence breast cancer progression. Here, we demonstrated in vitro and in vivo that low concentration of adiponectin at (1–5 μg/ml) induced a dicotomic pattern of effects on breast cancer growth, namely a stimulatory action in MCF‐7 cells, mediated by MAPK activation, and an inhibitory effect in MDA‐MB‐231 cells, through the activation of AMPK signaling. The latter signaling appeared markedly potentiated at higher concentration (20–30 μg/ml) in both cell types. In other words the modulatory effect of adiponectin may be driven by pMAPK/pAMPK ratio, which was enhanced at low concentrations in MCF‐7 cells, while it dropped markedly at higher doses in both cell types, supporting the inhibitory effect on cell growth. In addition, low doses of adiponectin induced a marked IGF‐IR phosphorylation. The latter event occurred at the same concentrations generally found in obese women. So, it is reasonable to postulate that in ERalpha‐positive cell line the well‐known IGF‐IR/ERalpha cross talk may activate MAPK, sustaining cell proliferation. Thus, on the basis of the present findings enhancing the circulating levels of adiponectin may represent an important target for novel therapeutic strategies in the treatment of this obesity‐associated malignancy. The research has been supported by AIRC MFAG 6180.