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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Bibliographic Details
Authors: Cedó Giné, Lídia, García León, Annabel, Baila Rueda, Lucía, Santos, David, Grijalva, Victor, Martínez Cignoni, Melanie Raquel, Carbó, José M., Metso, Jari, López Vilaró, Laura, Zorzano Olarte, Antonio, Valledor Fernández, Annabel, Cenarro, Ana, Jauhiainen, Matti, Lerma, Enrique, Fogelman, Alan M., Reddy, Srinivasa T., Escolà Gil, Joan Carles, Blanco-Vaca, Francisco
Format: article
Status:Published version
Publication Date:2016
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/118640
Online Access:https://hdl.handle.net/2445/118640
Access Level:Open access
Keyword:Càncer de mama
Hiperlipoproteïnes
Ratolins transgènics
Pèptids
Breast cancer
High density lipoproteins
Transgenic mice
Peptides
Description
Summary: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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