ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

Lídia Cedó, Annabel García-León, Lucía Baila-Rueda, David Santos, Victor Grijalva, Melanie Raquel Martínez-Cignoni, José M. Carbó, Jari Metso, Laura López-Vilaró, Antonio Zorzano, Annabel F. Valledor, Ana Cenarro, Matti Jauhiainen, Enrique Lerma, Alan M. Fogelman, Srinivasa T. Reddy, Joan Carles Escolà-Gil, Francisco Blanco-Vaca

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14 Citations (Scopus)

Abstract

© The Author(s) 2016. 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.
Original languageEnglish
Article number36387
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 3 Nov 2016

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