Limits...
YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells.

Sheng X, Li WB, Wang DL, Chen KH, Cao JJ, Luo Z, He J, Li MC, Liu WJ, Yu C - Mol Med Rep (2015)

Bottom Line: The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with para‑PCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002).The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022).Therefore, it was concluded that gene transcription and protein expression of YAP may be involved in the development of PCa, particularly CRPC, and may be a novel biomarker for investigation of the occurrence and progression of CRPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.

ABSTRACT
Yes-associated protein 65 (YAP65) has been implicated as an oncogene, and its expression is increased in human cancer. Previous studies have demonstrated that alterations in YAP activity may result in tumourigenesis of the prostate. With androgen deprivation therapies becoming progressively ineffective, often leading to life‑threatening androgen‑resistant prostate cancer (CRPC). The present study aimed to analyse the role of YAP in prostate cancer (PCa), particularly in CRPC. YAP protein was detected using immunohistochemistry and western blot analysis in different prostatic tissues. In addition, three specific RNA interference vectors targeting the human YAP gene were synthesised, and PC‑3 cells with a stable inhibition of YAP were obtained by transfection. MTT, flow cytometry, reverse transcription‑quantitative polymerase chain reaction and western blot assays were used to analyse the effects of YAP inhibition on the proliferation and apoptosis of PC‑3 cells. The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with para‑PCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002). The frequency of cells, which were positive for the expression of YAP exhibited a positive correlation (P=0.008) with the Gleason score, the tumour‑node‑metastasis staging (P=0.033) and the level of prostate specific antigens (P=0.0032) in PCa. The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022). The cell‑cycle of the transfected group was arrested in the G1 stage, which was detected using flow cytometry, and there was a significant increase in the apoptosis of cells in the transfected group (P=0.002). The mRNA and protein levels of TEA domain family member 1 were inhibited in the transfected group (P=0.001 and P=0.00, respectively). Therefore, it was concluded that gene transcription and protein expression of YAP may be involved in the development of PCa, particularly CRPC, and may be a novel biomarker for investigation of the occurrence and progression of CRPC. However, the mechanism underlying the modulation of YAP in CRPC remains to be fully elucidated.

Show MeSH

Related in: MedlinePlus

Correlation between YAP and Gleason score, TNM stage and PSA level using curve estimation regression analysis. (A) Correlation between YAP and Gleason score, in which a positive trend was observed between them. (B) Correlation between YAP and TNM stage. The integrating degree was not perfect between the linear and quadratic or cubic curve. (C) A positive correlation was also observed between YAP and PSA levels. PSA, prostate specific antigen; YAP, Yes-associated protein; TNM, tumour-node-metastasis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4581809&req=5

f2-mmr-12-04-4867: Correlation between YAP and Gleason score, TNM stage and PSA level using curve estimation regression analysis. (A) Correlation between YAP and Gleason score, in which a positive trend was observed between them. (B) Correlation between YAP and TNM stage. The integrating degree was not perfect between the linear and quadratic or cubic curve. (C) A positive correlation was also observed between YAP and PSA levels. PSA, prostate specific antigen; YAP, Yes-associated protein; TNM, tumour-node-metastasis.

Mentions: The frequencies of samples with positive expression of YAP among tissues with Gleason scores of <7, 7, and ≥8 were 50% (4/8), 72.7% (8/11), and 100% (13/13), respectively, revealing a positive correlation (P=0.008; Fig. 2A). Based on the TNM staging, the samples in which YAP was present exhibited an increasing trend between T1 and T4. For T1+T2 and T3+T4 stages, the frequencies were 60% (9/15) and 94.1% (16/17), respectively (P=0.033; Fig. 2B). The expression of YAP increased significantly with increasing PSA levels (<10 ng/ml vs. ≥10 ng/ml, P=0.0032; Table II, Fig. 2C).


YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells.

Sheng X, Li WB, Wang DL, Chen KH, Cao JJ, Luo Z, He J, Li MC, Liu WJ, Yu C - Mol Med Rep (2015)

Correlation between YAP and Gleason score, TNM stage and PSA level using curve estimation regression analysis. (A) Correlation between YAP and Gleason score, in which a positive trend was observed between them. (B) Correlation between YAP and TNM stage. The integrating degree was not perfect between the linear and quadratic or cubic curve. (C) A positive correlation was also observed between YAP and PSA levels. PSA, prostate specific antigen; YAP, Yes-associated protein; TNM, tumour-node-metastasis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581809&req=5

f2-mmr-12-04-4867: Correlation between YAP and Gleason score, TNM stage and PSA level using curve estimation regression analysis. (A) Correlation between YAP and Gleason score, in which a positive trend was observed between them. (B) Correlation between YAP and TNM stage. The integrating degree was not perfect between the linear and quadratic or cubic curve. (C) A positive correlation was also observed between YAP and PSA levels. PSA, prostate specific antigen; YAP, Yes-associated protein; TNM, tumour-node-metastasis.
Mentions: The frequencies of samples with positive expression of YAP among tissues with Gleason scores of <7, 7, and ≥8 were 50% (4/8), 72.7% (8/11), and 100% (13/13), respectively, revealing a positive correlation (P=0.008; Fig. 2A). Based on the TNM staging, the samples in which YAP was present exhibited an increasing trend between T1 and T4. For T1+T2 and T3+T4 stages, the frequencies were 60% (9/15) and 94.1% (16/17), respectively (P=0.033; Fig. 2B). The expression of YAP increased significantly with increasing PSA levels (<10 ng/ml vs. ≥10 ng/ml, P=0.0032; Table II, Fig. 2C).

Bottom Line: The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with para‑PCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002).The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022).Therefore, it was concluded that gene transcription and protein expression of YAP may be involved in the development of PCa, particularly CRPC, and may be a novel biomarker for investigation of the occurrence and progression of CRPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.

ABSTRACT
Yes-associated protein 65 (YAP65) has been implicated as an oncogene, and its expression is increased in human cancer. Previous studies have demonstrated that alterations in YAP activity may result in tumourigenesis of the prostate. With androgen deprivation therapies becoming progressively ineffective, often leading to life‑threatening androgen‑resistant prostate cancer (CRPC). The present study aimed to analyse the role of YAP in prostate cancer (PCa), particularly in CRPC. YAP protein was detected using immunohistochemistry and western blot analysis in different prostatic tissues. In addition, three specific RNA interference vectors targeting the human YAP gene were synthesised, and PC‑3 cells with a stable inhibition of YAP were obtained by transfection. MTT, flow cytometry, reverse transcription‑quantitative polymerase chain reaction and western blot assays were used to analyse the effects of YAP inhibition on the proliferation and apoptosis of PC‑3 cells. The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with para‑PCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002). The frequency of cells, which were positive for the expression of YAP exhibited a positive correlation (P=0.008) with the Gleason score, the tumour‑node‑metastasis staging (P=0.033) and the level of prostate specific antigens (P=0.0032) in PCa. The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022). The cell‑cycle of the transfected group was arrested in the G1 stage, which was detected using flow cytometry, and there was a significant increase in the apoptosis of cells in the transfected group (P=0.002). The mRNA and protein levels of TEA domain family member 1 were inhibited in the transfected group (P=0.001 and P=0.00, respectively). Therefore, it was concluded that gene transcription and protein expression of YAP may be involved in the development of PCa, particularly CRPC, and may be a novel biomarker for investigation of the occurrence and progression of CRPC. However, the mechanism underlying the modulation of YAP in CRPC remains to be fully elucidated.

Show MeSH
Related in: MedlinePlus