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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.

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Analysis of proliferation of cells in different groups using an MTT assay. Absorbance in yes-associated protein interference stable clones and NC group cells were counted for 7 days. Growth curves were plotted to assess the growth pattern of each cell line Data are expressed as the mean ± standard deviation. (P=0.022). NC, negative control.
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f5-mmr-12-04-4867: Analysis of proliferation of cells in different groups using an MTT assay. Absorbance in yes-associated protein interference stable clones and NC group cells were counted for 7 days. Growth curves were plotted to assess the growth pattern of each cell line Data are expressed as the mean ± standard deviation. (P=0.022). NC, negative control.

Mentions: To understand the physiological role of YAP, the expression of endogenous YAP was inhibited in the PC-3 cells. RT-qPCR and western blot analysis revealed that high expression levels of YAP in the PC-3 cells. To determine the effect of the expression of YAP on PC-3 cell growth, proliferation curves of the stable RNAi-YAP-1 interference clones were determined and compared with the corresponding NC (Fig. 5). The two-factor analysis of variance revealed that the difference between the two groups was statistically significant (P=0.022), based on the optical density value from the third day. The doubling times of the two groups were also significantly different, in which the transfected group exhibited a doubling time of 57.8 h, and the NC group exhibited a doubling time of 23.2 h (P=0.028).


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)

Analysis of proliferation of cells in different groups using an MTT assay. Absorbance in yes-associated protein interference stable clones and NC group cells were counted for 7 days. Growth curves were plotted to assess the growth pattern of each cell line Data are expressed as the mean ± standard deviation. (P=0.022). NC, negative control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5-mmr-12-04-4867: Analysis of proliferation of cells in different groups using an MTT assay. Absorbance in yes-associated protein interference stable clones and NC group cells were counted for 7 days. Growth curves were plotted to assess the growth pattern of each cell line Data are expressed as the mean ± standard deviation. (P=0.022). NC, negative control.
Mentions: To understand the physiological role of YAP, the expression of endogenous YAP was inhibited in the PC-3 cells. RT-qPCR and western blot analysis revealed that high expression levels of YAP in the PC-3 cells. To determine the effect of the expression of YAP on PC-3 cell growth, proliferation curves of the stable RNAi-YAP-1 interference clones were determined and compared with the corresponding NC (Fig. 5). The two-factor analysis of variance revealed that the difference between the two groups was statistically significant (P=0.022), based on the optical density value from the third day. The doubling times of the two groups were also significantly different, in which the transfected group exhibited a doubling time of 57.8 h, and the NC group exhibited a doubling time of 23.2 h (P=0.028).

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