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...

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Detalles Bibliográficos
Autores: Cedó, Lídia|||0000-0003-4354-3411, Garcia León, Annabel|||0000-0003-3007-9306, Baila-Rueda, Lucía, Santos, David|||0000-0003-1157-4969, Grijalva, Victor, Martínez Cignoni, Melanie Raquel|||0000-0002-3469-7980, Carbó, José María|||0000-0001-8301-5360, Metso, Jari, López Vilaró, Laura|||0000-0002-5428-8017, Zorzano Olarte, Antonio|||0000-0002-1638-0306, Valledor, Annabel F.|||0000-0003-4232-2633, Cenarro, Ana, Jauhiainen, Matti|||0000-0002-3836-3785, Lerma Puertas, Enrique|||0000-0001-7908-2747, Fogelman, Alan M., Reddy, Srinivasa T., Escolà-Gil, Joan Carles|||0000-0001-9021-2485, Blanco Vaca, Francisco|||0000-0001-7380-5385
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:203755
Acceso en línea:https://ddd.uab.cat/record/203755
https://dx.doi.org/urn:doi:10.1038/srep36387
Access Level:acceso abierto
Palabra clave:Animals
Antineoplastic Agents
Apolipoprotein A-I
Breast Neoplasms
Cell Proliferation
Cell Survival
Female
Humans
Lipoproteins, LDL
MCF-7 Cells
Mice
Mice, Transgenic
Molecular Mimicry
Peptides
Xenograft Model Antitumor Assays
Descripción
Sumario: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.

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