Progesterone regulation of tissue factor depends on MEK1/2 activation and requires the proline-rich site on progesterone receptor.
Endocrine
; 48(1): 309-20, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-24853881
To characterize the molecular mechanism and map the response element used by progesterone (P) to upregulate tissue factor (TF) in breast cancer cells. TF expression and mRNA levels were analyzed in breast cancer ZR-75 and T47D cells, using Western blot and real-time PCR, respectively. Mapping of the TF promoter was performed using luciferase vectors. Progesterone receptor (PR) and specificity protein 1 (Sp1) binding to the TF promoter were analyzed by chromatin immuno precipitation assay. Specific or selective inhibitors were used for the MEK1/2 and the c-Src pathways (UO126 and PP2, respectively). TF mRNA increase peaks at 18 h following P treatment in ZR-75 and T47D cells. P upregulation occurs via a transcriptional mechanism that depends on PR and MEK1/2 activation, PR and Sp1 transcription factors bind to a region in the TF promoter that contains three Sp1 sites. TF mRNA upregulation requires an intact PR proline-rich site (mPRO), but it is independent from c-Src. TF upregulation by P is mediated by Sp1 sites in the TF promoter region. Transcriptional upregulation in breast cancer cells occurs via a new mechanism that requires MEK1/2 activation and the mPRO site but independent of c-Src activity. PR Phosphorylation at serine 294 and 345 is not essential.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Progesterona
/
Tromboplastina
/
Prolina
/
Receptores de Progesterona
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Sistema de Sinalização das MAP Quinases
Limite:
Female
/
Humans
Idioma:
En
Revista:
Endocrine
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Chile