LDL-cholesterol signaling induces breast cancer proliferation and invasion

Lipids and cholesterol in particular, have long been associated with breast cancer (BC) onset and progression. However, the causative effects of elevated lipid levels and breast cancer remain largely undisclosed and were the subject of the present study. We took advantage of well-established in vitr...

Full description

Saved in:
Bibliographic Details
Published in:Lipids in health and disease Vol. 13; no. 1; p. 16
Main Authors: Rodrigues dos Santos, Catarina, Domingues, Germana, Matias, Inês, Matos, João, Fonseca, Isabel, de Almeida, José Mendes, Dias, Sérgio
Format: Journal Article
Language:English
Published: London BioMed Central 15.01.2014
BioMed Central Ltd
Springer Nature B.V
Subjects:
Analysis
Animals
Biomedical and Life Sciences
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Adhesion
Cell adhesion & migration
Cell growth
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cholesterol
Cholesterol, LDL - physiology
Clinical Nutrition
Development and progression
Diet, High-Fat - adverse effects
Disease prevention
Female
Gene Expression
Gene Expression Regulation, Neoplastic
Genotype & phenotype
Health aspects
Humans
Hypercholesterolemia
Life Sciences
Lipidology
Lipids
Lung Neoplasms - metabolism
Lung Neoplasms - secondary
Medical Biochemistry
Mice
Mice, Inbred BALB C
Mice, SCID
Neoplasm Invasiveness
Neoplasm Transplantation
Pathology
Protein Processing, Post-Translational
Signal Transduction
Software
Statins
Studies
Tumor Burden
Tumors
Tumor growth
LDL-cholesterol
Breast cancer
ISSN:1476-511X, 1476-511X
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Lipids and cholesterol in particular, have long been associated with breast cancer (BC) onset and progression. However, the causative effects of elevated lipid levels and breast cancer remain largely undisclosed and were the subject of the present study. We took advantage of well-established in vitro and in vivo models of cholesterol enrichment to exploit the mechanism involved in LDL-cholesterol favouring BC growth and invasiveness. We analyzed its effects in models that mimic different BC subtypes and stages. Our data show that LDL-cholesterol (but not HDL-cholesterol) promotes BC cells proliferation, migration and loss of adhesion, hallmarks of the epithelial to mesenchymal transition. In vivo studies modeling cholesterol levels showed that breast tumors are consistently larger and more proliferative in hypercholesterolemic mice, which also have more frequently lung metastases . Microarray analysis revealed an over expression of intermediates of Akt and ERK pathways suggesting a survival response induced by LDL, confirmed by WB analyses. Gene expression analysis also evidenced an activation of ErbB2 signaling pathway and decreased expression of adhesion molecules (cadherin-related family member3, CD226, Claudin 7 and Ocludin) in the cells exposed to LDL. Together, the present work shows novel mechanistic evidence that high LDL-cholesterol levels promote BC progression. These data provide rationale for the clinical control of cholesterol levels in BC patients.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:1476-511X
1476-511X
DOI:10.1186/1476-511X-13-16