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Inhibitory effect of adiponectin on breast cancer cell growth: evidences of the crucial role of ERα expression
Author(s) -
Mauro Loredana,
Pellegrino Michele,
De Amicis Francesca,
Giordano Cinzia,
Andò Sebastiano
Publication year - 2012
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.26.1_supplement.142.3
Subject(s) - downregulation and upregulation , biology , cyclin d1 , cancer research , estrogen receptor , cell cycle , cell growth , microbiology and biotechnology , endocrinology , breast cancer , cancer , gene , genetics
Adiponectin (adipo) has emerged as a possible link between obesity and breast cancer. Here, we demonstrated that adipo inhibited proliferation in ER‐negative cells, while stimulated growth in MCF‐7 cells. Adipo transactivated ERα in MCF‐7 cells and upregulated mRNA and protein content of the estrogen target gene cyclin D1 (CD1) involved in cell cycle progression. In contrast, in MDA‐MB‐231 cells adipo induced a downregulation of CD1 expression. The latter findings fitted with the opposite effects of adipo on CD1 promoter elicited in the two different cell lines. Mutagenesis studies and ChIP assays revealed that the Sp1 motif, present on CD1 promoter, was important for the modulatory role of adipo on CD1 promoter activity. In the presence of ERα, ChIP analysis revealed an increase in Sp1/ERα complex, concomitant with an enhanced Pol II and pCAF recruitment, addressing the involvement of an activator complex that mediated the adipo‐induced transcriptional activation of CD1. In contrast, in the absence of ERα, adipo exposure increased the recruitment of corepressors SMRT and NCoR and the association of HDAC‐1, that correlated with a significant decrease in Pol II on Sp1 site. Thus, we propose that the possible mechanism through which adipo may modulate CD1 expression affecting breast cancer growth is tightly related to the estrogen receptor dependency. The research has been supported by AIRC MFAG 6180.