Hyperglycemia enhances the proliferation of non-tumorigenic and malignant mammary epithelial cells through increased leptin/IGF1R signaling and activation of AKT/mTOR

Rebecca Lopez, Arunkumar Arumugam, Riya Joseph, Kanika Monga, Thiyagarajan Boopalan, Pamela Agullo, Christina Gutierrez, Sushmita Nandy, Ramadevi Subramani, Jose Manuel De La Rosa, Rajkumar Lakshmanaswamy

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Obesity and diabetes are associated with increased breast cancer risk and worse disease progression once cancer is diagnosed; however, the exact etiology behind these observations remains to be fully elucidated. Due to the global obesity/ diabetes pandemic, it is imperative to understand how these diseases promote and enhance breast cancer and other common cancers. In this study we demonstrate that hyperglycemia promotes breast cancer by altering leptin/IGF1R and AKT/mTOR signaling. To our knowledge, we show for the first time that in breast epithelial cells, hyperglycemia alone directly impacts leptin signaling. Hyperglycemia increased proliferation of both non-tumorigenic and malignant mammary epithelial cells. These observations coincided with increased leptin receptor and IGF1R receptor, as well as, increased levels of GRB2, pJAK2, pSTAT3, pIRS1/2, pAKT, and p-mTOR. Moreover, pJAK2 was almost completely colocalized with leptin receptor under high glucose conditions. These results demonstrate how hyperglycemia can potentially increase the risk of breast cancer in premalignant lesions and enhance cancer progression in malignant cells.

Original languageEnglish (US)
Article numbere79708
JournalPLoS ONE
Volume8
Issue number11
DOIs
StatePublished - Nov 18 2013

ASJC Scopus subject areas

  • General

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