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Down-regulation of PKCζ in renal cell carcinoma and its clinicopathological implications.

Pu YS, Huang CY, Chen JY, Kang WY, Lin YC, Shiu YS, Chuang SJ, Yu HJ, Lai MK, Tsai YC, Wu WJ, Hour TC - J. Biomed. Sci. (2012)

Bottom Line: Unfortunately, nearly all patients die of the metastatic and chemoresistant RCC.Interestingly, an increase of PKCζ expression was associated with the elevated tumor grade (P=0.04), but no such association was found in TNM stage (P=0.13).PKCζ expression was associated with tumorigenesis and chemoresistance in RCC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, National Taiwan University College of Medicine, Taipei, Taiwan.

ABSTRACT

Background: Metastatic renal cell carcinoma (RCC) is highly resistant to systemic chemotherapy. Unfortunately, nearly all patients die of the metastatic and chemoresistant RCC. Recent studies have shown the atypical PKCζ is an important regulator of tumorigenesis. However, the correlation between PKCζ expression and the clinical outcome in RCC patients is unclear. We examined the level of PKCζ expression in human RCC.

Methods: PKCζ mRNA and protein expressions were examined by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) respectively in RCC tissues of 144 patients. Cellular cytotoxicity and proliferation were assessed by MTT.

Results: PKCζ expression was significantly higher in normal than in cancerous tissues (P<0.0001) by real-time PCR and IHC. Similarly, PKCζ expression was down-regulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. Interestingly, an increase of PKCζ expression was associated with the elevated tumor grade (P=0.04), but no such association was found in TNM stage (P=0.13). Tumors with higher PKCζ expression were associated with tumor size (P=0.048). Expression of higher PKCζ found a poor survival in patients with high tumor grade. Down-regulation of PKCζ showed the significant chemoresistance in RCC cell lines. Inactivation of PKCζ expression enhanced cellular resistance to cisplatin and paclitaxel, and proliferation in HK-2 cells by specific PKCζ siRNA and inhibitor.

Conclusions: PKCζ expression was associated with tumorigenesis and chemoresistance in RCC.

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Down-regulation of PKCζ showed the higher chemoresistance in RCC cell lines. (A) PKCζ protein expression in HK-2 and 4 RCC cell lines by Western blotting. α-tubulin was used as an internal control. (B) The intensity of PKCζ protein in figure 4(A) was examined by densitometer analysis. Fold changes were normalized against the expression of PKCζ protein in HK-2 cells. Chemosensivity of HK-2, 786-O and ACHN cells to (C) cisplatin and (D) paclitaxel were examined by MTT assay, respectively.
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Figure 4: Down-regulation of PKCζ showed the higher chemoresistance in RCC cell lines. (A) PKCζ protein expression in HK-2 and 4 RCC cell lines by Western blotting. α-tubulin was used as an internal control. (B) The intensity of PKCζ protein in figure 4(A) was examined by densitometer analysis. Fold changes were normalized against the expression of PKCζ protein in HK-2 cells. Chemosensivity of HK-2, 786-O and ACHN cells to (C) cisplatin and (D) paclitaxel were examined by MTT assay, respectively.

Mentions: PKCζ protein levels were significantly reduced in the four RCC cell lines compared to HK-2 the benign immortalized cell line by Western blotting (Figure 4A and 4B), respectively. Similarly, PKCζ gene levels were decreased in these RCC cell lines as estimated (data not shown). We identified the molecular role of PKCζ in RCC cells. The higher expression of PKCζ in HK-2 was with higher sensitivity to cisplatin and paclitaxel than in the 786-O and ACHN cell lines, respectively (Figure 4C and 4D).


Down-regulation of PKCζ in renal cell carcinoma and its clinicopathological implications.

Pu YS, Huang CY, Chen JY, Kang WY, Lin YC, Shiu YS, Chuang SJ, Yu HJ, Lai MK, Tsai YC, Wu WJ, Hour TC - J. Biomed. Sci. (2012)

Down-regulation of PKCζ showed the higher chemoresistance in RCC cell lines. (A) PKCζ protein expression in HK-2 and 4 RCC cell lines by Western blotting. α-tubulin was used as an internal control. (B) The intensity of PKCζ protein in figure 4(A) was examined by densitometer analysis. Fold changes were normalized against the expression of PKCζ protein in HK-2 cells. Chemosensivity of HK-2, 786-O and ACHN cells to (C) cisplatin and (D) paclitaxel were examined by MTT assay, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376037&req=5

Figure 4: Down-regulation of PKCζ showed the higher chemoresistance in RCC cell lines. (A) PKCζ protein expression in HK-2 and 4 RCC cell lines by Western blotting. α-tubulin was used as an internal control. (B) The intensity of PKCζ protein in figure 4(A) was examined by densitometer analysis. Fold changes were normalized against the expression of PKCζ protein in HK-2 cells. Chemosensivity of HK-2, 786-O and ACHN cells to (C) cisplatin and (D) paclitaxel were examined by MTT assay, respectively.
Mentions: PKCζ protein levels were significantly reduced in the four RCC cell lines compared to HK-2 the benign immortalized cell line by Western blotting (Figure 4A and 4B), respectively. Similarly, PKCζ gene levels were decreased in these RCC cell lines as estimated (data not shown). We identified the molecular role of PKCζ in RCC cells. The higher expression of PKCζ in HK-2 was with higher sensitivity to cisplatin and paclitaxel than in the 786-O and ACHN cell lines, respectively (Figure 4C and 4D).

Bottom Line: Unfortunately, nearly all patients die of the metastatic and chemoresistant RCC.Interestingly, an increase of PKCζ expression was associated with the elevated tumor grade (P=0.04), but no such association was found in TNM stage (P=0.13).PKCζ expression was associated with tumorigenesis and chemoresistance in RCC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, National Taiwan University College of Medicine, Taipei, Taiwan.

ABSTRACT

Background: Metastatic renal cell carcinoma (RCC) is highly resistant to systemic chemotherapy. Unfortunately, nearly all patients die of the metastatic and chemoresistant RCC. Recent studies have shown the atypical PKCζ is an important regulator of tumorigenesis. However, the correlation between PKCζ expression and the clinical outcome in RCC patients is unclear. We examined the level of PKCζ expression in human RCC.

Methods: PKCζ mRNA and protein expressions were examined by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) respectively in RCC tissues of 144 patients. Cellular cytotoxicity and proliferation were assessed by MTT.

Results: PKCζ expression was significantly higher in normal than in cancerous tissues (P<0.0001) by real-time PCR and IHC. Similarly, PKCζ expression was down-regulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. Interestingly, an increase of PKCζ expression was associated with the elevated tumor grade (P=0.04), but no such association was found in TNM stage (P=0.13). Tumors with higher PKCζ expression were associated with tumor size (P=0.048). Expression of higher PKCζ found a poor survival in patients with high tumor grade. Down-regulation of PKCζ showed the significant chemoresistance in RCC cell lines. Inactivation of PKCζ expression enhanced cellular resistance to cisplatin and paclitaxel, and proliferation in HK-2 cells by specific PKCζ siRNA and inhibitor.

Conclusions: PKCζ expression was associated with tumorigenesis and chemoresistance in RCC.

Show MeSH
Related in: MedlinePlus