Downregulation of Rap1Gap: A Switch from DCIS to Invasive Breast Carcinoma via ERK/MAPK Activation

Neoplasia : an International Journal for Oncology Research
Seema ShahRaymond R Mattingly

Abstract

Diagnosis of breast ductal carcinoma in situ (DCIS) presents a challenge since we cannot yet distinguish those cases that would remain indolent and not require aggressive treatment from cases that may progress to invasive ductal cancer (IDC). The purpose of this study is to determine the role of Rap1Gap, a GTPase activating protein, in the progression from DCIS to IDC. Immunohistochemistry (IHC) analysis of samples from breast cancer patients shows an increase in Rap1Gap expression in DCIS compared to normal breast tissue and IDCs. In order to study the mechanisms of malignant progression, we employed an in vitro three-dimensional (3D) model that more accurately recapitulates both structural and functional cues of breast tissue. Immunoblotting results show that Rap1Gap levels in MCF10.Ca1D cells (a model of invasive carcinoma) are reduced compared to those in MCF10.DCIS (a model of DCIS). Retroviral silencing of Rap1Gap in MCF10.DCIS cells activated extracellular regulated kinase (ERK) mitogen-activated protein kinase (MAPK), induced extensive cytoskeletal reorganization and acquisition of mesenchymal phenotype, and enhanced invasion. Enforced reexpression of Rap1Gap in MCF10.DCIS-Rap1GapshRNA cells reduced Rap1 activity and re...Continue Reading

Citations

Jul 30, 2018·Journal of Mammary Gland Biology and Neoplasia·Ethan J BrockBonnie F Sloane
Apr 15, 2019·Journal of Molecular Neuroscience : MN·Ciqing YangJuntang Lin
Sep 11, 2020·Biomedicines·Chin-King LooiChun-Wai Mai
Jul 24, 2021·Biomarkers in Medicine·Xuan ChenYongqing Lai
Jul 27, 2021·Cytogenetic and Genome Research·Bita FaamMahmoud Hashemi Tabar

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Methods Mentioned

BETA
GTPase
transfection
Infection
transfections
protein assay
pull down
pulldowns
xenograft

Software Mentioned

Indica TMA
Volocity
GraphPad Prism
ImageJ

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