Centro Investigación en Educación Superior

Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

AUTOR(ES): Marcelo A. Villagran /Francisco A. Gutierrez-Castro / Diego F. Pantoja /Jose C. Alarcon / Macarena A. Farina / Romina F. Amigo / Natalia A. Munoz-Godoy / Mabel G. Pinilla / Eduardo A. Pena / Ivan Gonzalez-Chavarria / Jorge R. Toledo / Coralia I. Rivas / Juan C. Vera / Eileen M. McNerney / Sergio A. Onate.
Licencia Creative Commons Reconocimiento CC BY. Esta obra está bajo una Licencia Creative Commons Reconocimiento CC BY 4.0 Internacional.

Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced ARmediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in ARmediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells.

Documentos relacionados

Centro Investigación en Educación Superior

Evaluación preoperatoria y predictores de morbimortalidad en resección de cáncer de pulmón

Surgical resection of lung cancer, the only available curative option today, is strongly associated with mortality. The goal during the […]

Centro Investigación en Educación Superior

Over‑expression of muscle glycogen synthase in human diabetic nephropathy

Diabetic nephropathy (DN) is a major complication of diabetic patients and the leading cause of end-stage renal disease. Glomerular dysfunction plays a critical role in DN, […]

Centro Investigación en Educación Superior

Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia

Maternal physiological hypercholesterolemia occurs during pregnancy, ensuring normal fetal development. In some cases, the maternal plasma cholesterol level increases to above this physiological range, leading to maternal supraphysiological hypercholesterolemia (MSPH). This […]

Saltar a la barra de herramientas