[Expression analysis of NOTCH1/HES1/PTEN signaling pathway in invasive bladder transitional cell carcinoma].
OBJECTIVE
To explore the role of NOTCH1/HES1/PTEN signaling pathway in invasive TCCB (bladder transitional cell carcinoma).


METHODS
The expressions of NOTCH1, HES1 and PTEN were detected in 36 cases of invasive TCCB tissues and 10 cases of normal bladder samples by real-time q-polymerase chain reaction (q-PCR) and Western blot. Then NOTCH1-ORF plasmid and its blank vector pCMV6-Entry were transfected into T24 cell respectively. And the expressions of three above-mentioned target genes were measured by real-time q-PCR and Western blot. Furthermore, cell proliferation, cell apoptosis and cell cycle were analyzed respectively by MTS assay and flow cytometry.


RESULTS
Compared with normal bladder samples, the higher levels of both mRNA and protein of NOTCH1 and HES1 were detected in invasive TCCB tissues while there was a lower expression of PTEN (P < 0.05). The mRNA expression levels of NOTCH1 and HES1 were 4.22 and 3.75 folds respectively higher than those of normal tissues. In NOTCH1-overexpressed T24 cell, the expression of HES1 was 5.43 folds higher than that of the blank vector control group while the expression of PTEN declined to 41.76% (P < 0.01). MTS assay showed that the NOTCH1-ORF transfection obviously promoted cell proliferation in T24 cell (P < 0.01).


CONCLUSIONS
NOTCH1 gene may function as an oncogene by regulating HES1/PTEN in invasive TCCB and its aberrant activation promotes cell proliferation.
Department of Urology, Chinese PLA General Hospital, Beijing 100853, China.
Jin
J
Sima
Ming-yang
MY
Zhu
Qing
Q
Ai
Chao
C
Zhang
Zhi-yong
ZY
Yao
Qing-bo
QB
Huang
Xu
X
Zhang
D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D051059:PTEN Phosphohydrolase; D012333:RNA, Messenger; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C497761:NOTCH1 protein, human; C078493:HES1 protein, human; C494929:PTEN protein, human