Oncotarget

Research Papers:

Stat3 accelerates Myc induced tumor formation while reducing growth rate in a mouse model of breast cancer

Jing-Ru Jhan, Eran R. Andrechek _

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Abstract

Jing-Ru Jhan1, Eran R. Andrechek1

1Department of Physiology, Michigan State University, East Lansing, MI 48824, USA

Correspondence to:

Eran R. Andrechek, email: andrech1@msu.edu

Keywords: breast cancer, mammary gland, Myc, Stat3, tumor latency

Received: May 31, 2016     Accepted: August 13, 2016     Published: August 29, 2016

ABSTRACT

Elevated Myc expression has been noted in basal breast cancer but therapies targeting Myc directly are lacking. It is therefore critical to characterize the interaction of Myc with other genes and pathways to uncover future potential therapeutic strategies. In this study, we bioinformatically predicted a role for Stat3 in Myc induced mammary tumors and tested it using mouse models. During normal mammary function, loss of Stat3 in Myc transgenic dams resulted in lethality of pups due to lactation deficiencies. We also observed that deletion of Stat3 in the mammary glands of MMTV-Myc mice unexpectedly resulted in increased and earlier hyperplasia and expedited tumorigenesis. However, despite arising earlier, Myc tumors lacking Stat3 grew more slowly with alterations in the resulting histological subtypes, including a dramatic increase in EMT-like tumors. We also observed that these tumors had impaired angiogenesis and a slight decrease in lung metastases. This metastatic finding is distinct from previously published findings in both MMTV-Neu and MMTV-PyMT mouse models. Together, the literature and our current research demonstrate that Stat3 can function as an oncogene or as a tumor repressor depending on the oncogenic driver and developmental context.

Author Information

Jing-Ru Jhan

Eran R. Andrechek
Primary Contact  _


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