Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis

The mechanisms by which mammary carcinomas acquire hormone independence are still unknown. To study the role of cancer-associated fibroblasts (CAF) in the acquisition of hormone-independence we used a hormone-dependent (HD) mouse mammary tumor and its hormone-independent (HI) variant, which grows in...

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Autores principales:	Giulianelli, S., Cerliani, J.P., Lamb, C.A., Fabris, V.T., Bottino, M.C., Gorostiaga, M.A., Novaro, V., Góngora, A., Baldi, A., Molinolo, A., Lanari, C.
Formato:	JOUR
Materias:	Carcinoma associated fibroblasts FGF receptors Fibroblast growth factor 2 Hormone dependence Progesterone receptors and breast cancer 1 tert butyl 3 [6 (3,5 dimethoxyphenyl) 2 (4 diethylaminobutylamino)pyrido[2,3 d]pyrimidin 7 yl]urea antigestagen estrogen receptor fibroblast growth factor 2 fibroblast growth factor receptor 2 medroxyprogesterone acetate mifepristone progesterone receptor animal cell animal experiment animal model animal tissue article breast carcinoma cancer associated fibroblast cancer cell cancer growth cell culture cell proliferation cell viability coculture controlled study disease association DNA binding epithelium cell female fibroblast gel mobility shift assay hormonal regulation hormone dependence hormone response immunofluorescence immunohistochemistry mouse nonhuman priority journal protein expression Western blotting Animals Breast Neoplasms Cell Proliferation Cells, Cultured Coculture Techniques Female Fibroblast Growth Factor 2 Fibroblasts Gene Expression Regulation, Neoplastic Humans Mice Mice, Inbred BALB C Progesterone Protein Binding Protein Kinase Inhibitors Receptor, Fibroblast Growth Factor, Type 2 Receptors, Progesterone RNA, Small Interfering Signal Transduction
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00207136_v123_n11_p2518_Giulianelli
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00207136_v123_n11_p2518_Giulianelli2023-10-03T14:18:23Z Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis Giulianelli, S. Cerliani, J.P. Lamb, C.A. Fabris, V.T. Bottino, M.C. Gorostiaga, M.A. Novaro, V. Góngora, A. Baldi, A. Molinolo, A. Lanari, C. Carcinoma associated fibroblasts FGF receptors Fibroblast growth factor 2 Hormone dependence Progesterone receptors and breast cancer 1 tert butyl 3 [6 (3,5 dimethoxyphenyl) 2 (4 diethylaminobutylamino)pyrido[2,3 d]pyrimidin 7 yl]urea antigestagen estrogen receptor fibroblast growth factor 2 fibroblast growth factor receptor 2 medroxyprogesterone acetate mifepristone progesterone receptor animal cell animal experiment animal model animal tissue article breast carcinoma cancer associated fibroblast cancer cell cancer growth cell culture cell proliferation cell viability coculture controlled study disease association DNA binding epithelium cell female fibroblast gel mobility shift assay hormonal regulation hormone dependence hormone response immunofluorescence immunohistochemistry mouse nonhuman priority journal protein expression Western blotting Animals Breast Neoplasms Cell Proliferation Cells, Cultured Coculture Techniques Female Fibroblast Growth Factor 2 Fibroblasts Gene Expression Regulation, Neoplastic Humans Mice Mice, Inbred BALB C Progesterone Protein Binding Protein Kinase Inhibitors Receptor, Fibroblast Growth Factor, Type 2 Receptors, Progesterone RNA, Small Interfering Signal Transduction The mechanisms by which mammary carcinomas acquire hormone independence are still unknown. To study the role of cancer-associated fibroblasts (CAF) in the acquisition of hormone-independence we used a hormone-dependent (HD) mouse mammary tumor and its hormone-independent (HI) variant, which grows in vivo without hormone supply. HI tumors express higher levels of FGFR-2 than HD tumors. In spite of their in vivo differences, both tumors have the same hormone requirement in primary cultures. We demonstrated that CAF from HI tumors (CAF-HI) growing in vitro, express higher levels of FGF-2 than HD counterparts (CAF-HD). FGF-2 activated the progesterone receptors (PR) in the tumor cells, thus increasing cell proliferation in both HI and HD tumors. CAF-HI induced a higher proliferative rate on the tumor cells and in PR activation than CAF-HD. The blockage of FGF-2 in the co-cultures or the genetic or pharmacological inhibition of FGFR-2 inhibited PR activation and tumor cell proliferation. Moreover, in vivo, the FGFR inhibitor decreased C4-HI tumor growth, whereas FGF-2 was able to stimulate C4-HD tumor growth as MPA. T47D human breast cancer cells were also stimulated by progestins, FGF-2 or CAF-HI, and this stimulation was abrogated by antiprogestins, suggesting that the murine C4-HI cells respond as the human T47D cells. In summary, this is the first study reporting differences between CAF from HD and HI tumors suggesting that CAF-HI actively participate in driving HI tumor growth. © 2008 Wiley-Liss, Inc. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00207136_v123_n11_p2518_Giulianelli
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Carcinoma associated fibroblasts FGF receptors Fibroblast growth factor 2 Hormone dependence Progesterone receptors and breast cancer 1 tert butyl 3 [6 (3,5 dimethoxyphenyl) 2 (4 diethylaminobutylamino)pyrido[2,3 d]pyrimidin 7 yl]urea antigestagen estrogen receptor fibroblast growth factor 2 fibroblast growth factor receptor 2 medroxyprogesterone acetate mifepristone progesterone receptor animal cell animal experiment animal model animal tissue article breast carcinoma cancer associated fibroblast cancer cell cancer growth cell culture cell proliferation cell viability coculture controlled study disease association DNA binding epithelium cell female fibroblast gel mobility shift assay hormonal regulation hormone dependence hormone response immunofluorescence immunohistochemistry mouse nonhuman priority journal protein expression Western blotting Animals Breast Neoplasms Cell Proliferation Cells, Cultured Coculture Techniques Female Fibroblast Growth Factor 2 Fibroblasts Gene Expression Regulation, Neoplastic Humans Mice Mice, Inbred BALB C Progesterone Protein Binding Protein Kinase Inhibitors Receptor, Fibroblast Growth Factor, Type 2 Receptors, Progesterone RNA, Small Interfering Signal Transduction
spellingShingle	Carcinoma associated fibroblasts FGF receptors Fibroblast growth factor 2 Hormone dependence Progesterone receptors and breast cancer 1 tert butyl 3 [6 (3,5 dimethoxyphenyl) 2 (4 diethylaminobutylamino)pyrido[2,3 d]pyrimidin 7 yl]urea antigestagen estrogen receptor fibroblast growth factor 2 fibroblast growth factor receptor 2 medroxyprogesterone acetate mifepristone progesterone receptor animal cell animal experiment animal model animal tissue article breast carcinoma cancer associated fibroblast cancer cell cancer growth cell culture cell proliferation cell viability coculture controlled study disease association DNA binding epithelium cell female fibroblast gel mobility shift assay hormonal regulation hormone dependence hormone response immunofluorescence immunohistochemistry mouse nonhuman priority journal protein expression Western blotting Animals Breast Neoplasms Cell Proliferation Cells, Cultured Coculture Techniques Female Fibroblast Growth Factor 2 Fibroblasts Gene Expression Regulation, Neoplastic Humans Mice Mice, Inbred BALB C Progesterone Protein Binding Protein Kinase Inhibitors Receptor, Fibroblast Growth Factor, Type 2 Receptors, Progesterone RNA, Small Interfering Signal Transduction Giulianelli, S. Cerliani, J.P. Lamb, C.A. Fabris, V.T. Bottino, M.C. Gorostiaga, M.A. Novaro, V. Góngora, A. Baldi, A. Molinolo, A. Lanari, C. Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis
topic_facet	Carcinoma associated fibroblasts FGF receptors Fibroblast growth factor 2 Hormone dependence Progesterone receptors and breast cancer 1 tert butyl 3 [6 (3,5 dimethoxyphenyl) 2 (4 diethylaminobutylamino)pyrido[2,3 d]pyrimidin 7 yl]urea antigestagen estrogen receptor fibroblast growth factor 2 fibroblast growth factor receptor 2 medroxyprogesterone acetate mifepristone progesterone receptor animal cell animal experiment animal model animal tissue article breast carcinoma cancer associated fibroblast cancer cell cancer growth cell culture cell proliferation cell viability coculture controlled study disease association DNA binding epithelium cell female fibroblast gel mobility shift assay hormonal regulation hormone dependence hormone response immunofluorescence immunohistochemistry mouse nonhuman priority journal protein expression Western blotting Animals Breast Neoplasms Cell Proliferation Cells, Cultured Coculture Techniques Female Fibroblast Growth Factor 2 Fibroblasts Gene Expression Regulation, Neoplastic Humans Mice Mice, Inbred BALB C Progesterone Protein Binding Protein Kinase Inhibitors Receptor, Fibroblast Growth Factor, Type 2 Receptors, Progesterone RNA, Small Interfering Signal Transduction
description	The mechanisms by which mammary carcinomas acquire hormone independence are still unknown. To study the role of cancer-associated fibroblasts (CAF) in the acquisition of hormone-independence we used a hormone-dependent (HD) mouse mammary tumor and its hormone-independent (HI) variant, which grows in vivo without hormone supply. HI tumors express higher levels of FGFR-2 than HD tumors. In spite of their in vivo differences, both tumors have the same hormone requirement in primary cultures. We demonstrated that CAF from HI tumors (CAF-HI) growing in vitro, express higher levels of FGF-2 than HD counterparts (CAF-HD). FGF-2 activated the progesterone receptors (PR) in the tumor cells, thus increasing cell proliferation in both HI and HD tumors. CAF-HI induced a higher proliferative rate on the tumor cells and in PR activation than CAF-HD. The blockage of FGF-2 in the co-cultures or the genetic or pharmacological inhibition of FGFR-2 inhibited PR activation and tumor cell proliferation. Moreover, in vivo, the FGFR inhibitor decreased C4-HI tumor growth, whereas FGF-2 was able to stimulate C4-HD tumor growth as MPA. T47D human breast cancer cells were also stimulated by progestins, FGF-2 or CAF-HI, and this stimulation was abrogated by antiprogestins, suggesting that the murine C4-HI cells respond as the human T47D cells. In summary, this is the first study reporting differences between CAF from HD and HI tumors suggesting that CAF-HI actively participate in driving HI tumor growth. © 2008 Wiley-Liss, Inc.
format	JOUR
author	Giulianelli, S. Cerliani, J.P. Lamb, C.A. Fabris, V.T. Bottino, M.C. Gorostiaga, M.A. Novaro, V. Góngora, A. Baldi, A. Molinolo, A. Lanari, C.
author_facet	Giulianelli, S. Cerliani, J.P. Lamb, C.A. Fabris, V.T. Bottino, M.C. Gorostiaga, M.A. Novaro, V. Góngora, A. Baldi, A. Molinolo, A. Lanari, C.
author_sort	Giulianelli, S.
title	Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis
title_short	Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis
title_full	Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis
title_fullStr	Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis
title_full_unstemmed	Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis
title_sort	carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: a role for the fgf-2/fgfr-2 axis
url	http://hdl.handle.net/20.500.12110/paper_00207136_v123_n11_p2518_Giulianelli
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Carcinoma-associated fibroblasts activate progesterone receptors and induce hormone independent mammary tumor growth: A role for the FGF-2/FGFR-2 axis

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