ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer
Por:
Cedo, L, Garcia-Leon, A, Baila-Rueda, L, Santos, D, Grijalva, V, Martinez-Cignoni, MR, Carbo, JM, Metso, J, Lopez-Vilaro, L, Zorzano, A, Valledor, AF, Cenarro, A, Jauhiainen, M, Lerma, E, Fogelman, AM, Reddy, ST, Escola-Gil, JC, Blanco-Vaca, F
Publicada:
3 nov 2016
Resumen:
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.
Filiaciones:
Cedo, L:
Inst Invest Biomed IIB St Pau, Barcelona, Spain
CIBERDEM, CIBER Diabet & Enfermedades Metabol Asociadas, Barcelona, Spain
Garcia-Leon, A:
Inst Invest Biomed IIB St Pau, Barcelona, Spain
Baila-Rueda, L:
Hosp Univ Miguel Servet, Inst Invest Sanitaria Aragon, Unidad Clin & Invest Lipidos & Arteriosclerosis, Zaragoza, Spain
Santos, D:
Inst Invest Biomed IIB St Pau, Barcelona, Spain
CIBERDEM, CIBER Diabet & Enfermedades Metabol Asociadas, Barcelona, Spain
Grijalva, V:
Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA
Martinez-Cignoni, MR:
Inst Invest Biomed IIB St Pau, Barcelona, Spain
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Barcelona, Spain
Carbo, JM:
Univ Barcelona, Sch Biol, Dept Cell Biol Physiol & Immunol, Nucl Receptor Grp, Barcelona, Spain
Metso, J:
Natl Inst Hlth & Welf, Genom & Biomarkers Unit, Helsinki, Finland
Minerva Fdn, Biomedicum, Helsinki, Finland
Lopez-Vilaro, L:
Inst Invest Biomed IIB St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Dept Patol, Barcelona, Spain
Zorzano, A:
CIBERDEM, CIBER Diabet & Enfermedades Metabol Asociadas, Barcelona, Spain
Inst Res Biomed IRB Barcelona, Barcelona, Spain
Valledor, AF:
Univ Barcelona, Sch Biol, Dept Cell Biol Physiol & Immunol, Nucl Receptor Grp, Barcelona, Spain
Cenarro, A:
Hosp Univ Miguel Servet, Inst Invest Sanitaria Aragon, Unidad Clin & Invest Lipidos & Arteriosclerosis, Zaragoza, Spain
Jauhiainen, M:
Natl Inst Hlth & Welf, Genom & Biomarkers Unit, Helsinki, Finland
Minerva Fdn, Biomedicum, Helsinki, Finland
Lerma, E:
Inst Invest Biomed IIB St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Dept Patol, Barcelona, Spain
Univ Autonoma Barcelona, Dept Ciencies Morfol, Barcelona, Spain
Fogelman, AM:
Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA
Reddy, ST:
Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA
Escola-Gil, JC:
Inst Invest Biomed IIB St Pau, Barcelona, Spain
CIBERDEM, CIBER Diabet & Enfermedades Metabol Asociadas, Barcelona, Spain
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Barcelona, Spain
Blanco-Vaca, F:
Inst Invest Biomed IIB St Pau, Barcelona, Spain
CIBERDEM, CIBER Diabet & Enfermedades Metabol Asociadas, Barcelona, Spain
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, Barcelona, Spain
Gold, Green Published
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