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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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The prognostic survival of PKCζ in RCC. (A) High tumor grade was associated with short survival time in RCC patients. Tumor grade III was significantly associated with poorer outcome than grade I (P = 0.032) and II (P = 0.016) on 5-year survival, respectively. (B) High expression of PKCζ was associated with poorer clinical prognosis. The ratio of PKCζ expression (cancer/normal ratio) was PKCζ score of cancer compared with normal tissue from the same patient. The median value of all RCC patients was 0.54. PKCζ ratio > 0.54 had significantly poor survival than ratio ≤ 0.54 on 5-year survival in RCC (P = 0.042).
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Figure 3: The prognostic survival of PKCζ in RCC. (A) High tumor grade was associated with short survival time in RCC patients. Tumor grade III was significantly associated with poorer outcome than grade I (P = 0.032) and II (P = 0.016) on 5-year survival, respectively. (B) High expression of PKCζ was associated with poorer clinical prognosis. The ratio of PKCζ expression (cancer/normal ratio) was PKCζ score of cancer compared with normal tissue from the same patient. The median value of all RCC patients was 0.54. PKCζ ratio > 0.54 had significantly poor survival than ratio ≤ 0.54 on 5-year survival in RCC (P = 0.042).

Mentions: We evaluate the relationship between tumor grade and 5-year survival in a population of patients with RCC. As shown in Figure 3A, the tumor grade III was significantly associated with poor outcome than grade I (P = 0.032) and II (P = 0.016) on 5-year survival, respectively. Thus, higher expression of PKCζ was associated with short survival time in RCC patients with higher tumor grade. However, grade IV showed no significant 5-year survival between grade I and grade II. The ratio of PKCζ expression (cancer/normal ratio) was PKCζ score of cancer compared with normal tissue from the same patient. The median value of all RCC patients was 0.54. Interestingly, we found the PKCζ ratio > 0.54 had significantly poor survival than ratio ≤ 0.54 on 5-year survival in RCC (P = 0.042) (Figure 3B).


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)

The prognostic survival of PKCζ in RCC. (A) High tumor grade was associated with short survival time in RCC patients. Tumor grade III was significantly associated with poorer outcome than grade I (P = 0.032) and II (P = 0.016) on 5-year survival, respectively. (B) High expression of PKCζ was associated with poorer clinical prognosis. The ratio of PKCζ expression (cancer/normal ratio) was PKCζ score of cancer compared with normal tissue from the same patient. The median value of all RCC patients was 0.54. PKCζ ratio > 0.54 had significantly poor survival than ratio ≤ 0.54 on 5-year survival in RCC (P = 0.042).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: The prognostic survival of PKCζ in RCC. (A) High tumor grade was associated with short survival time in RCC patients. Tumor grade III was significantly associated with poorer outcome than grade I (P = 0.032) and II (P = 0.016) on 5-year survival, respectively. (B) High expression of PKCζ was associated with poorer clinical prognosis. The ratio of PKCζ expression (cancer/normal ratio) was PKCζ score of cancer compared with normal tissue from the same patient. The median value of all RCC patients was 0.54. PKCζ ratio > 0.54 had significantly poor survival than ratio ≤ 0.54 on 5-year survival in RCC (P = 0.042).
Mentions: We evaluate the relationship between tumor grade and 5-year survival in a population of patients with RCC. As shown in Figure 3A, the tumor grade III was significantly associated with poor outcome than grade I (P = 0.032) and II (P = 0.016) on 5-year survival, respectively. Thus, higher expression of PKCζ was associated with short survival time in RCC patients with higher tumor grade. However, grade IV showed no significant 5-year survival between grade I and grade II. The ratio of PKCζ expression (cancer/normal ratio) was PKCζ score of cancer compared with normal tissue from the same patient. The median value of all RCC patients was 0.54. Interestingly, we found the PKCζ ratio > 0.54 had significantly poor survival than ratio ≤ 0.54 on 5-year survival in RCC (P = 0.042) (Figure 3B).

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