In vivo and in vitro estrogenic and progestagenic actions of Tibolone

Estrogen and progestin combination in hormone replacement therapy (HRT) increases the incidence of breast cancer, but decreases the endometrial cancer risk of unopposed estrogen. Therefore, a SERM such as Tibolone, that delivers the beneficial, but not the adverse side effects, of steroid hormones w...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	SADARANGANI,ANIL, SALGADO,ANA MARÍA, KATO,SUMIE, PINTO,MAURICIO, CARVAJAL,ANDRÉS, MONSO,CAROLINA, OWEN,GARETH I, VIGIL,PILAR
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2005
Materias:	breast/endometrium cancer estrogenic HRT progestagenic & tibolone
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602005000200014
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:scielo:S0716-97602005000200014
record_format	dspace
spelling	oai:scielo:S0716-976020050002000142007-01-04In vivo and in vitro estrogenic and progestagenic actions of TiboloneSADARANGANI,ANILSALGADO,ANA MARÍAKATO,SUMIEPINTO,MAURICIOCARVAJAL,ANDRÉSMONSO,CAROLINAOWEN,GARETH IVIGIL,PILAR breast/endometrium cancer estrogenic HRT progestagenic & tibolone Estrogen and progestin combination in hormone replacement therapy (HRT) increases the incidence of breast cancer, but decreases the endometrial cancer risk of unopposed estrogen. Therefore, a SERM such as Tibolone, that delivers the beneficial, but not the adverse side effects, of steroid hormones would be clinically advantageous. However, data from the Million Women Study suggests that Tibolone increases the risk of both breast and endometrial cancer. Herein, we assessed the estrogenic and progestagenic actions of Tibolone using transvaginal sonography studies and an in vitro model of breast (ZR-75, MCF7) and endometrial cancer (Ishikawa). The known cancer associated proteins (ER, EGFR, STAT5, tissue factor and Bcl-xL) were selected for study. Transvaginal sonography demonstrated that postmenopausal women treated with Tibolone displayed a thinner endometrium than in the late proliferative phase, but had a phenotype characteristic of the secretory phase, thus demonstrating the estrogenic and progestagenic actions of this SERM. In vitro, Tibolone acted as an estrogen in downregulating ER and upregulating Bcl-xL, yet as progesterone, increasing STAT5 and tissue factor in breast cancer cells. The increase in tissue factor by Tibolone correlated with its coagulative potential. Interestingly, EGFR was up-regulated by progesterone in the breast and by estrogen in endometrial cells, while Tibolone increased protein levels in both cell types. In conclusion, this study further demonstrates the estrogenic and progestagenic nature of Tibolone. The pattern of regulation of known oncogenes in cells of breast and endometrial origin dictates caution and vigilance in the prescription of Tibolone and subsequent patient monitoringinfo:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.38 n.2-3 20052005-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602005000200014en10.4067/S0716-97602005000200014
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	breast/endometrium cancer estrogenic HRT progestagenic & tibolone
spellingShingle	breast/endometrium cancer estrogenic HRT progestagenic & tibolone SADARANGANI,ANIL SALGADO,ANA MARÍA KATO,SUMIE PINTO,MAURICIO CARVAJAL,ANDRÉS MONSO,CAROLINA OWEN,GARETH I VIGIL,PILAR In vivo and in vitro estrogenic and progestagenic actions of Tibolone
description	Estrogen and progestin combination in hormone replacement therapy (HRT) increases the incidence of breast cancer, but decreases the endometrial cancer risk of unopposed estrogen. Therefore, a SERM such as Tibolone, that delivers the beneficial, but not the adverse side effects, of steroid hormones would be clinically advantageous. However, data from the Million Women Study suggests that Tibolone increases the risk of both breast and endometrial cancer. Herein, we assessed the estrogenic and progestagenic actions of Tibolone using transvaginal sonography studies and an in vitro model of breast (ZR-75, MCF7) and endometrial cancer (Ishikawa). The known cancer associated proteins (ER, EGFR, STAT5, tissue factor and Bcl-xL) were selected for study. Transvaginal sonography demonstrated that postmenopausal women treated with Tibolone displayed a thinner endometrium than in the late proliferative phase, but had a phenotype characteristic of the secretory phase, thus demonstrating the estrogenic and progestagenic actions of this SERM. In vitro, Tibolone acted as an estrogen in downregulating ER and upregulating Bcl-xL, yet as progesterone, increasing STAT5 and tissue factor in breast cancer cells. The increase in tissue factor by Tibolone correlated with its coagulative potential. Interestingly, EGFR was up-regulated by progesterone in the breast and by estrogen in endometrial cells, while Tibolone increased protein levels in both cell types. In conclusion, this study further demonstrates the estrogenic and progestagenic nature of Tibolone. The pattern of regulation of known oncogenes in cells of breast and endometrial origin dictates caution and vigilance in the prescription of Tibolone and subsequent patient monitoring
author	SADARANGANI,ANIL SALGADO,ANA MARÍA KATO,SUMIE PINTO,MAURICIO CARVAJAL,ANDRÉS MONSO,CAROLINA OWEN,GARETH I VIGIL,PILAR
author_facet	SADARANGANI,ANIL SALGADO,ANA MARÍA KATO,SUMIE PINTO,MAURICIO CARVAJAL,ANDRÉS MONSO,CAROLINA OWEN,GARETH I VIGIL,PILAR
author_sort	SADARANGANI,ANIL
title	In vivo and in vitro estrogenic and progestagenic actions of Tibolone
title_short	In vivo and in vitro estrogenic and progestagenic actions of Tibolone
title_full	In vivo and in vitro estrogenic and progestagenic actions of Tibolone
title_fullStr	In vivo and in vitro estrogenic and progestagenic actions of Tibolone
title_full_unstemmed	In vivo and in vitro estrogenic and progestagenic actions of Tibolone
title_sort	in vivo and in vitro estrogenic and progestagenic actions of tibolone
publisher	Sociedad de Biología de Chile
publishDate	2005
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602005000200014
work_keys_str_mv	AT sadaranganianil invivoandinvitroestrogenicandprogestagenicactionsoftibolone AT salgadoanamaria invivoandinvitroestrogenicandprogestagenicactionsoftibolone AT katosumie invivoandinvitroestrogenicandprogestagenicactionsoftibolone AT pintomauricio invivoandinvitroestrogenicandprogestagenicactionsoftibolone AT carvajalandres invivoandinvitroestrogenicandprogestagenicactionsoftibolone AT monsocarolina invivoandinvitroestrogenicandprogestagenicactionsoftibolone AT owengarethi invivoandinvitroestrogenicandprogestagenicactionsoftibolone AT vigilpilar invivoandinvitroestrogenicandprogestagenicactionsoftibolone
_version_	1718441389052657664

In vivo and in vitro estrogenic and progestagenic actions of Tibolone

Ejemplares similares