Basal-like breast cancer: modeling its initiation and characterizing novel EGFR variants
type: CreativeWork
description: Breast cancer (BC) is now a disease that will affect 1 out of every 8 women worldwide. Due to its highly heterogeneous nature, BC is usually further classified into different subtypes according to gene expression profiling analysis. Basal-like breast cancer (BBC) accounts for 15-20% of all cases of BC. BBC is very aggressive, highly metastatic, and often lethal, mostly due to our poor understanding of the key genetic events that lead to the onset and/or maintain this subtype of BC. As a result, we currently lack targeted therapies that are otherwise very effective in some of the better understood subtypes of BC. Therefore we set to work on deciphering the genetic alterations that when, expressed altogether, would model the onset of sporadic BBC in human cell lines. We already know that patients with BBC often display mutations in the tumor suppressor p53, as well as over-expression of the epidermal growth factor receptor (EGFR) protein by immunohistochemistry, and that loss of PTEN protein is also seen occurring along with the aforementioned lesions. However, there is no model for sporadic BBC that accurately reflects the genetic changes that BBC tumor samples display for studying this BC subtype progression and/or providing a base for which pharmacological studies can be done to find an effective therapy. Thus we used a non-transformed immortalized mammary epithelial cell line, MCF10A, as our model and engineered cells with termed 'triple modified' cells that express the three aforementioned alterations (PTEN, EGFR, p53) that highly observed in BBC. Furthermore, as part of the goal to better understand the genetic underpinnings that occur in BBC progression, we investigated whether variant forms of EGFR existed in cell lines of the basal-like subtype. Prior studies have demonstrated that immunostaining for EGFR in BBC patient tumor samples is elevated, though the molecular mechanisms are not well understood. EGFR is only amplified in BBC in less than 1% of cases th…
abstract: Breast cancer (BC) is now a disease that will affect 1 out of every 8 women worldwide. Due to its highly heterogeneous nature, BC is usually further classified into different subtypes according to gene expression profiling analysis. Basal-like breast cancer (BBC) accounts for 15-20% of all cases of BC. BBC is very aggressive, highly metastatic, and often lethal, mostly due to our poor understanding of the key genetic events that lead to the onset and/or maintain this subtype of BC. As a result, we currently lack targeted therapies that are otherwise very effective in some of the better understood subtypes of BC. Therefore we set to work on deciphering the genetic alterations that when, expressed altogether, would model the onset of sporadic BBC in human cell lines. We already know that patients with BBC often display mutations in the tumor suppressor p53, as well as over-expression of the epidermal growth factor receptor (EGFR) protein by immunohistochemistry, and that loss of PTEN protein is also seen occurring along with the aforementioned lesions. However, there is no model for sporadic BBC that accurately reflects the genetic changes that BBC tumor samples display for studying this BC subtype progression and/or providing a base for which pharmacological studies can be done to find an effective therapy. Thus we used a non-transformed immortalized mammary epithelial cell line, MCF10A, as our model and engineered cells with termed 'triple modified' cells that express the three aforementioned alterations (PTEN, EGFR, p53) that highly observed in BBC. Furthermore, as part of the goal to better understand the genetic underpinnings that occur in BBC progression, we investigated whether variant forms of EGFR existed in cell lines of the basal-like subtype. Prior studies have demonstrated that immunostaining for EGFR in BBC patient tumor samples is elevated, though the molecular mechanisms are not well understood. EGFR is only amplified in BBC in less than 1% of cases th…
author: Pires, Maira Moura
language: English
keywords: Biology, Oncology, Breast--Cancer, Tumor suppressor proteins, Carcinogenesis
date published: 2012
date modified: 2026-07-24T01:44:23Z
provider: Columbia University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Columbia University

PropertyValue
property ID: DOI
value: 10.7916/D81J9HW4