Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas
To explore mechanisms related to hormone resistance, three resistant variants of the MPA mouse breast cancer tumor model with low levels of progesterone receptor (PR) isoform A (PR-A)/high PR-B expression were developed by prolonged selective pressure with antiprogestins. The resistant phenotype of...
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2009
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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v116_n3_p449_Wargon http://hdl.handle.net/20.500.12110/paper_01676806_v116_n3_p449_Wargon |
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paper:paper_01676806_v116_n3_p449_Wargon2023-06-08T15:16:41Z Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas Acquired hormone resistance AKT Antiprogestins Breast cancer De novo hormone resistance ERK Estrogen receptors Hormone resistance Metastasis Progesterone receptor isoforms Tumor regression estradiol estrogen receptor alpha lonaprisan mifepristone mitogen activated protein kinase 1 mitogen activated protein kinase 3 progesterone receptor A progesterone receptor B protein kinase B tamoxifen hormone antagonist isoprotein mifepristone mitogen activated protein kinase 1 mitogen activated protein kinase 3 progesterone receptor progesterone receptor A progesterone receptor B protein kinase B animal experiment animal model animal tissue article axillary lymph node breast cancer breast carcinoma cancer inhibition cancer resistance controlled study female lymph node metastasis metastasis potential mouse nonhuman priority journal tumor growth animal Bagg albino mouse cell proliferation drug resistance experimental neoplasm fluorescent antibody technique metabolism pathology survival rate Western blotting Animals Blotting, Western Cell Proliferation Drug Resistance, Neoplasm Female Fluorescent Antibody Technique Hormone Antagonists Lymphatic Metastasis Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mifepristone Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Protein Isoforms Proto-Oncogene Proteins c-akt Receptors, Progesterone Survival Rate To explore mechanisms related to hormone resistance, three resistant variants of the MPA mouse breast cancer tumor model with low levels of progesterone receptor (PR) isoform A (PR-A)/high PR-B expression were developed by prolonged selective pressure with antiprogestins. The resistant phenotype of one tumor line was reversed spontaneously after several consecutive passages in syngeneic BALB/c mice or by 17-b-estradiol or tamoxifen treatment, and this reversion was significantly associated with an increase in PR-A expression. The responsive parental tumors disclosed low activation of ERK and high activation of AKT; resistant tumors on the other hand, showed the opposite, and this was associated with a higher metastatic potential, that did not revert. This study shows for the first time in vivo a relationship between PR isoform expression and antiprogestin responsiveness, demonstrating that, whereas acquired resistance may be reversed, changes in kinase activation and metastatic potential are unidirectional associated with tumor progression. © Springer Science+Business Media, LLC. 2008. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v116_n3_p449_Wargon http://hdl.handle.net/20.500.12110/paper_01676806_v116_n3_p449_Wargon |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Acquired hormone resistance AKT Antiprogestins Breast cancer De novo hormone resistance ERK Estrogen receptors Hormone resistance Metastasis Progesterone receptor isoforms Tumor regression estradiol estrogen receptor alpha lonaprisan mifepristone mitogen activated protein kinase 1 mitogen activated protein kinase 3 progesterone receptor A progesterone receptor B protein kinase B tamoxifen hormone antagonist isoprotein mifepristone mitogen activated protein kinase 1 mitogen activated protein kinase 3 progesterone receptor progesterone receptor A progesterone receptor B protein kinase B animal experiment animal model animal tissue article axillary lymph node breast cancer breast carcinoma cancer inhibition cancer resistance controlled study female lymph node metastasis metastasis potential mouse nonhuman priority journal tumor growth animal Bagg albino mouse cell proliferation drug resistance experimental neoplasm fluorescent antibody technique metabolism pathology survival rate Western blotting Animals Blotting, Western Cell Proliferation Drug Resistance, Neoplasm Female Fluorescent Antibody Technique Hormone Antagonists Lymphatic Metastasis Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mifepristone Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Protein Isoforms Proto-Oncogene Proteins c-akt Receptors, Progesterone Survival Rate |
spellingShingle |
Acquired hormone resistance AKT Antiprogestins Breast cancer De novo hormone resistance ERK Estrogen receptors Hormone resistance Metastasis Progesterone receptor isoforms Tumor regression estradiol estrogen receptor alpha lonaprisan mifepristone mitogen activated protein kinase 1 mitogen activated protein kinase 3 progesterone receptor A progesterone receptor B protein kinase B tamoxifen hormone antagonist isoprotein mifepristone mitogen activated protein kinase 1 mitogen activated protein kinase 3 progesterone receptor progesterone receptor A progesterone receptor B protein kinase B animal experiment animal model animal tissue article axillary lymph node breast cancer breast carcinoma cancer inhibition cancer resistance controlled study female lymph node metastasis metastasis potential mouse nonhuman priority journal tumor growth animal Bagg albino mouse cell proliferation drug resistance experimental neoplasm fluorescent antibody technique metabolism pathology survival rate Western blotting Animals Blotting, Western Cell Proliferation Drug Resistance, Neoplasm Female Fluorescent Antibody Technique Hormone Antagonists Lymphatic Metastasis Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mifepristone Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Protein Isoforms Proto-Oncogene Proteins c-akt Receptors, Progesterone Survival Rate Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas |
topic_facet |
Acquired hormone resistance AKT Antiprogestins Breast cancer De novo hormone resistance ERK Estrogen receptors Hormone resistance Metastasis Progesterone receptor isoforms Tumor regression estradiol estrogen receptor alpha lonaprisan mifepristone mitogen activated protein kinase 1 mitogen activated protein kinase 3 progesterone receptor A progesterone receptor B protein kinase B tamoxifen hormone antagonist isoprotein mifepristone mitogen activated protein kinase 1 mitogen activated protein kinase 3 progesterone receptor progesterone receptor A progesterone receptor B protein kinase B animal experiment animal model animal tissue article axillary lymph node breast cancer breast carcinoma cancer inhibition cancer resistance controlled study female lymph node metastasis metastasis potential mouse nonhuman priority journal tumor growth animal Bagg albino mouse cell proliferation drug resistance experimental neoplasm fluorescent antibody technique metabolism pathology survival rate Western blotting Animals Blotting, Western Cell Proliferation Drug Resistance, Neoplasm Female Fluorescent Antibody Technique Hormone Antagonists Lymphatic Metastasis Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mifepristone Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Protein Isoforms Proto-Oncogene Proteins c-akt Receptors, Progesterone Survival Rate |
description |
To explore mechanisms related to hormone resistance, three resistant variants of the MPA mouse breast cancer tumor model with low levels of progesterone receptor (PR) isoform A (PR-A)/high PR-B expression were developed by prolonged selective pressure with antiprogestins. The resistant phenotype of one tumor line was reversed spontaneously after several consecutive passages in syngeneic BALB/c mice or by 17-b-estradiol or tamoxifen treatment, and this reversion was significantly associated with an increase in PR-A expression. The responsive parental tumors disclosed low activation of ERK and high activation of AKT; resistant tumors on the other hand, showed the opposite, and this was associated with a higher metastatic potential, that did not revert. This study shows for the first time in vivo a relationship between PR isoform expression and antiprogestin responsiveness, demonstrating that, whereas acquired resistance may be reversed, changes in kinase activation and metastatic potential are unidirectional associated with tumor progression. © Springer Science+Business Media, LLC. 2008. |
title |
Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas |
title_short |
Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas |
title_full |
Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas |
title_fullStr |
Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas |
title_full_unstemmed |
Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas |
title_sort |
reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas |
publishDate |
2009 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v116_n3_p449_Wargon http://hdl.handle.net/20.500.12110/paper_01676806_v116_n3_p449_Wargon |
_version_ |
1768546249138503680 |