Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation

Progestin regulation of gene expression was assessed in the progestin-dependent murine tumor line C4HD which requires MPA, a synthetic progestin, for in vivo growth and expresses high levels of progesterone receptor (PR). By using suppressive subtractive hybridization, caveolin-1 was identified as a...

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Detalles Bibliográficos
Autores principales: Salatino, M., Beguelin, W., Peters, M.G., Carnevale, R., Proietti, C.J., Galigniana, M.D., Vedoy, C.G., Schillaci, R., Charreau, E.H., Sogayar, M.C., Elizalde, P.V.
Formato: JOUR
Materias:
Breast cancer
Caveolin-1
Progesterone receptor
antisense oligodeoxynucleotide
caveolin 1
gestagen
medroxyprogesterone acetate
messenger RNA
mifepristone
mitogen activated protein kinase
phosphatidylinositol 3 kinase
progesterone receptor
tyrosine
animal cell
animal experiment
article
breast cancer
cancer cell
cell activation
cell culture
cell growth
cell proliferation
cell stimulation
confocal microscopy
controlled study
DNA responsive element
female
gene expression
human
human cell
immunoprecipitation
in vitro study
mouse
nonhuman
Northern blotting
oncogene src
priority journal
protein expression
protein phosphorylation
receptor upregulation
suppression subtractive hybridization
Western blotting
1-Phosphatidylinositol 3-Kinase
Amino Acid Sequence
Animals
Base Sequence
Caveolin 1
Female
Gene Expression Regulation, Neoplastic
Mammary Neoplasms, Experimental
MAP Kinase Signaling System
Medroxyprogesterone 17-Acetate
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Phosphorylation
Promoter Regions (Genetics)
Receptors, Progesterone
src-Family Kinases
Murinae
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_09509232_v25_n59_p7723_Salatino
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Progestin regulation of gene expression was assessed in the progestin-dependent murine tumor line C4HD which requires MPA, a synthetic progestin, for in vivo growth and expresses high levels of progesterone receptor (PR). By using suppressive subtractive hybridization, caveolin-1 was identified as a gene whose expression was increased with in vivo MPA treatment. By Northern and Western blot analysis, we further confirmed that caveolin-1 mRNA and protein expression increased in MPA-treated tumors as compared with untreated tumors. When primary cultures of C4HD cells were treated in vitro with MPA, caveolin-1 levels also increased, effect that was abolished by pre-treatment with progestin antagonist RU486. In addition, MPA promoted strong caveolin-1 promoter transcriptional activation both in mouse and human breast cancer cells. We also showed that MPA regulation of caveolin-1 expression involved in activation of two signaling pathways: MAPK and PI-3K. Short-term MPA treatment of C4HD cells led to tyrosine phosphorylation of caveolin-1 protein, where Src was the kinase involved. Additionally, we showed that MPA-induced association of caveolin-1 and PR, which was detected by coimmunoprecipitation and by confocal microscopy. Finally, we proved that MPA-induced proliferation of C4HD cells was inhibited by suppression of caveolin-1 expression with antisense oligodeoxynucleotides to caveolin-1 mRNA. Furthermore, we observed that inhibition of caveolin-1 expression abrogated PR capacity to induced luciferase activity from a progesterone response element-driven reporter plasmid. Comprehensively, our results demonstrated for the first time that caveolin-1 expression is upregulated by progestin in breast cancer. We also demonstrated that caveolin-1 is a downstream effector of MPA that is partially responsible for the stimulation of growth of breast cancer cells. © 2006 Nature Publishing Group All rights reserved.

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