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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todo:paper_09509232_v25_n59_p7723_Salatino2023-10-03T15:50:30Z Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation 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. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09509232_v25_n59_p7723_Salatino |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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. Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
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. |
| author_facet |
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. |
| author_sort |
Salatino, M. |
| title |
Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation |
| title_short |
Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation |
| title_full |
Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation |
| title_fullStr |
Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation |
| title_full_unstemmed |
Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation |
| title_sort |
progestin-induced caveolin-1 expression mediates breast cancer cell proliferation |
| url |
http://hdl.handle.net/20.500.12110/paper_09509232_v25_n59_p7723_Salatino |
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