ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer.
Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification.
Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain.|CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain.
Lídia
L
Cedó
Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain.
Annabel
A
García-León
Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.
Lucía
L
Baila-Rueda
Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain.|CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain.
David
D
Santos
Department of Medicine, University of California, Los Angeles, CA, USA.
Victor
V
Grijalva
Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain.|Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain.
Melanie Raquel
MR
Martínez-Cignoni
Nuclear Receptor Group, Department of Cell Biology, Physiology and Immunology, School of Biology, University of Barcelona, Barcelona, Spain.
José M
JM
Carbó
National Institute for Health and Welfare, Genomics and Biomarkers Unit, and Minerva Foundation Institute for Medical Research, Biomedicum, Helsinki, Finland.
Jari
J
Metso
Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain.|Departament de Patologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Laura
L
López-Vilaró
CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain.|Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
Antonio
A
Zorzano
Nuclear Receptor Group, Department of Cell Biology, Physiology and Immunology, School of Biology, University of Barcelona, Barcelona, Spain.
Annabel F
AF
Valledor
Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.
Ana
A
Cenarro
National Institute for Health and Welfare, Genomics and Biomarkers Unit, and Minerva Foundation Institute for Medical Research, Biomedicum, Helsinki, Finland.
Matti
M
Jauhiainen
Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain.|Departament de Patologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.|Departament de Ciències Morfològiques, Universitat Autònoma de Barcelona, Barcelona, Spain.
Enrique
E
Lerma
Department of Medicine, University of California, Los Angeles, CA, USA.
Alan M
AM
Fogelman
Department of Medicine, University of California, Los Angeles, CA, USA.
Srinivasa T
ST
Reddy
Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain.|CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain.|Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain.
Joan Carles
JC
Escolà-Gil
Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain.|CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain.|Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain.
Francisco
F
Blanco-Vaca
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000737:chemistry*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D061986:MCF-7 Cells; D051379:Mice; D008822:Mice, Transgenic; D018716:Molecular Mimicry; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D016632:Apolipoprotein A-I; D008077:Lipoproteins, LDL; D010455:Peptides; C099252:oxidized low density lipoprotein