Expression and clinical significance of Notch receptors in human renal cell carcinoma.
OBJECTIVE
The pathological roles of Notch receptors in renal cell carcinoma (RCC) are still unclear, although Notch receptors have been shown to have an effect on many malignant tumours. Therefore, in this study, we examined the patterns of expression and clinical significance of Notch receptors in RCC.


METHODS
Eighty-four cases of renal cell carcinoma tissues were detected by immunohistochemistry. Eleven paired fresh surgical renal cell carcinoma and adjacent non-neoplastic renal samples were analysed by Western blot and reverse transcriptase polymerase chain reaction. In addition, the expression of Notch receptors in renal cancer cell lines (A498 and 786-O) and human normal kidney tubule epithelial cell lines (HK-2 and HKC) were analysed by Western blot.


RESULTS
The expression levels of Notch1 and Notch4 were absent or significantly decreased in renal cell carcinoma tissues compared with the adjacent non-neoplastic tissues [Notch1: 22.6% (19/84) versus 78.7% (59/75); Notch4: 27.4% (23/84) versus 73.3% (55/75); p < 0.05). Moreover, the levels of expression of Notch1 and Notch4 were also markedly down-regulated in human renal cancer cell lines. Notch1 was negatively correlated with tumour stage, while Notch4 expression had no significant association with pathological parameters. The levels of expression of Notch2 and Notch3 were minimally detected in tumours and non-neoplastic tissues.


CONCLUSIONS
Our findings indicated that the expression of Notch receptors was deregulated and Notch signalling might play an important role in the progress of renal cell carcinoma.
Sun
Shiren
S
State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
Du
Rui
R
Gao
Juan
J
Ning
Xiaoxuan
X
Xie
Huahong
H
Lin
Xia
X
Liu
Jie
J
Fan
Daiming
D
D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D051881:Receptor, Notch1 / Q000096:biosynthesis*; D051883:Receptor, Notch2 / Q000096:biosynthesis*; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; C499374:NOTCH3 protein, human; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D051880:Receptors, Notch