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Ppar gamma 1 Facilitates ErbB2-Mammary Adenocarcinoma in Mice
Journal article   Open access   Peer reviewed

Ppar gamma 1 Facilitates ErbB2-Mammary Adenocarcinoma in Mice

Xuanmao Jiao, Lifeng Tian, Zhao Zhang, Joanna Balcerek, Andrew V. Kossenkov, Mathew C. Casimiro, Chenguang Wang, Yichuan Liu, Adam Ertel, Raymond E. Soccio, …
Cancers, v 13(9)
01 May 2021
DOI: https://doi.org/10.3390/cancers13092171
PMID: 33946495
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.3390/cancers13092171View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Life Sciences & Biomedicine Oncology Science & Technology
Simple Summary: HER2, which is associated with clinically aggressive disease, is overexpressed in 15-20% of breast cancers (BC). Peroxisome proliferator-activated receptor gamma (PPAR gamma), is expressed in a variety of malignancies. The aim of our study was to determine the function of endogenous Ppar gamma 1 in the onset and progression of mammary tumors induced by ErbB2 in mice. Genetic deletion of Ppar gamma 1 slowed the rate of tumor progression and death from ErbB2-induced mammary tumors. The deletion of Ppar gamma 1 correlated with reduced pro-tumorigenic inflammation. We conclude ErbB2 collaborates with endogenous Ppar gamma 1 in the onset and progression of mammary tumorigenesis. HER2, which is associated with clinically aggressive disease, is overexpressed in 15-20% of breast cancers (BC). The host immune system participates in the therapeutic response of HER2(+) breast cancer. Identifying genetic programs that participate in ErbB2-induced tumors may provide the rational basis for co-extinction therapeutic approaches. Peroxisome proliferator-activated receptor gamma (PPAR gamma), which is expressed in a variety of malignancies, governs biological functions through transcriptional programs. Herein, genetic deletion of endogenous Ppar gamma 1 restrained mammary tumor progression, lipogenesis, and induced local mammary tumor macrophage infiltration, without affecting other tissue hematopoietic stem cell pools. Endogenous Ppar gamma 1 induced expression of both an EphA2-Amphiregulin and an inflammatory INF gamma and Cxcl5 signaling module, that was recapitulated in human breast cancer. Ppar gamma 1 bound directly to growth promoting and proinflammatory target genes in the context of chromatin. We conclude Ppar gamma 1 promotes ErbB2-induced tumor growth and inflammation and represents a relevant target for therapeutic coextinction. Herein, endogenous Ppar gamma 1 promoted ErbB2-mediated mammary tumor onset and progression. PPAR gamma 1 increased expression of an EGF-EphA2 receptor tyrosine kinase module and a cytokine/chemokine 1 transcriptional module. The induction of a pro-tumorigenic inflammatory state by Ppar gamma 1 may provide the rationale for complementary coextinction programs in ErbB2 tumors.

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6 citations in Web of Science
6 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Oncology
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