Evidence that leptin up-regulates E-cadherin expression in breast cancer: Effects on tumor growth and progression

Loredana Mauro, Stefania Catalano, Gianluca Bossi, Michele Pellegrino, Ines Barone, Sara Morales, Cinzia Giordano, Viviana Bartella, Ivan Casaburi, Sebastiano Andò

Research output: Contribution to journalArticle

Abstract

Leptin, a cytokine mainly produced by adipocytes, seems to play a crucial role in mammary carcinogenesis. In the present study, we explored the mechanism of leptin-mediated promotion of breast tumor growth using xenograft MCF-7 in 45-day-old female nude mice, and an in vitro model represented by MCF-7 three-dimensional cultures. Xenograft tumors, obtained only in animals with estradiol (E2) pellet implants, doubled control value after 13 weeks of leptin exposure. In three-dimensional cultures, leptin and/or E2 enhanced cell-cell adhesion. This increased aggregation seems to be dependent on E-cadherin because it was completely abrogated in the presence of function-blocking E-cadherin antibody or EGTA, a calcium-chelating agent. In three-dimensional cultures, leptin and/or E2 treatment significantly increased cell growth, which was abrogated when E-cadherin function was blocked. These findings well correlated with an increase of mRNA and protein content of E-cadherin in three-dimensional cultures and in xenografts. In MCF-7 cells both hormones were able to activate E-cadherin promoter. Mutagenesis studies, electrophoretic mobility shift assay, and chromatin immunoprecipitation assays revealed that cyclic AMP-responsive element binding protein and Sp1 motifs, present on E-cadherin promoter, were important for the up-regulatory effects induced by both hormones on E-cadherin expression in breast cancer MCF-7 cells. In conclusion, the present study shows how leptin is able to promote tumor cell proliferation and homotypic tumor cell adhesion via an increase of E-cadherin expression. This combined effect may give reasonable emphasis to the important role of this cytokine in stimulating primary breast tumor cell growth and progression, particularly in obese women.

Original languageEnglish
Pages (from-to)3412-3421
Number of pages10
JournalCancer Research
Volume67
Issue number7
DOIs
Publication statusPublished - Apr 1 2007

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Evidence that leptin up-regulates E-cadherin expression in breast cancer: Effects on tumor growth and progression'. Together they form a unique fingerprint.

  • Cite this

    Mauro, L., Catalano, S., Bossi, G., Pellegrino, M., Barone, I., Morales, S., Giordano, C., Bartella, V., Casaburi, I., & Andò, S. (2007). Evidence that leptin up-regulates E-cadherin expression in breast cancer: Effects on tumor growth and progression. Cancer Research, 67(7), 3412-3421. https://doi.org/10.1158/0008-5472.CAN-06-2890