title: Stat3 accelerates Myc induced tumor formation while reducing growth rate in a mouse model of breast cancer.
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.
authors: Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
authors: Jing-Ru
authors: JR
authors: Jhan
authors: Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
authors: Eran R
authors: ER
authors: Andrechek
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000502:physiology*
chemical_list: C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse
keywords: Myc; Stat3; breast cancer; mammary gland; tumor latency