A-Kinase Anchoring Protein 13 (AKAP13) Augments Progesterone Signaling in Uterine Fibroid Cells.
J Clin Endocrinol Metab
; 104(3): 970-980, 2019 03 01.
Article
in En
| MEDLINE
| ID: mdl-30239831
ABSTRACT
Context Uterine leiomyomata (fibroids) are prevalent sex hormoneâdependent tumors with an altered response to mechanical stress. Ulipristal acetate, a selective progesterone receptor (PR) modulator, significantly reduces fibroid size in patients. However, PR signaling in fibroids and its relationship to mechanical signaling are incompletely understood. Objective:
Our prior studies revealed that A-kinase anchoring protein 13 (AKAP13) was overexpressed in fibroids and contributed to altered mechanotransduction in fibroids. Because AKAP13 augmented nuclear receptor signaling in other tissues, we sought to determine whether AKAP13 might influence PR signaling in fibroids. Methods andResults:
Fibroid samples from patients treated with ulipristal acetate or placebo were examined for AKAP13 expression by using immunohistochemistry. In immortalized uterine fibroid cell lines and COS-7 cells, we observed that AKAP13 increased ligand-dependent PR activation of luciferase reporters and endogenous progesterone-responsive genes for PR-B but not PR-A. Inhibition of ERK reduced activation of PR-dependent signaling by AKAP13, but inhibition of p38 MAPK had no effect. In addition, glutathione S-transferaseâbinding assays revealed that AKAP13 was bound to PR-B through its carboxyl terminus.Conclusion:
These data suggest an intersection of mechanical signaling and PR signaling involving AKAP13 through ERK. Further elucidation of the integration of mechanical and hormonal signaling pathways in fibroids may provide insight into fibroid development and suggest new therapeutic strategies for treatment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Uterine Neoplasms
/
Receptors, Progesterone
/
Minor Histocompatibility Antigens
/
Proto-Oncogene Proteins
/
A Kinase Anchor Proteins
/
Leiomyoma
Type of study:
Clinical_trials
Limits:
Adult
/
Animals
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2019
Document type:
Article