Contributions of the RhoA guanine nucleotide exchange factor Net1 to polyoma middle T antigen-mediated mammary gland tumorigenesis and metastasis

Breast Cancer Research : BCR
Yan ZuoJeffrey A Frost

Abstract

The RhoA activating protein Net1 contributes to breast cancer cell proliferation, motility, and invasion in vitro, yet little is known about its roles in mammary gland tumorigenesis and metastasis. Net1 knockout (KO) mice were bred to mice with mammary gland specific expression of the polyoma middle T antigen (PyMT) oncogene. Mammary gland tumorigenesis and lung metastasis were monitored. Individual tumors were assessed for proliferation, apoptosis, angiogenesis, RhoA activation, and activation of PyMT-dependent signaling pathways. Primary tumor cells from wild-type and Net1 KO mice were transplanted into the mammary glands of wild-type, nontumor-bearing mice, and tumor growth and metastasis were assessed. Gene expression in wild-type and Net1 KO tumors was analyzed by gene ontology enrichment and for relative activation of gene expression signatures indicative of signaling pathways important for breast cancer initiation and progression. A gene expression signature indicative of Net1 function was identified. Human breast cancer gene expression profiles were screened for the presence of a Net1 gene expression signature. We show that Net1 makes fundamental contributions to mammary gland tumorigenesis and metastasis. Net1 deletion...Continue Reading

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Citations

Aug 28, 2019·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Wei ZongRongrong Jing
Aug 21, 2019·Oncogene·Julius H Svensmark, Cord Brakebusch
Jul 9, 2020·Computational and Structural Biotechnology Journal·Jocelyn GalEmmanuel Chamorey
Feb 7, 2021·Biomolecules·Chibin ChengEnmin Li
Oct 17, 2020·Proceedings of the National Academy of Sciences of the United States of America·George ChrisafisStavroula Mili

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Methods Mentioned

BETA
GTPases
GTPase
nucleotide exchange
pulldowns

Software Mentioned

Axiovision
NIS
GATHER
Illumina GenomeStudio
Elements Basic Research

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