PMID- 16896691
OWN - NLM
STAT- MEDLINE
DCOM- 20070118
LR  - 20181113
IS  - 0300-5623 (Print)
IS  - 0300-5623 (Linking)
VI  - 34
IP  - 5
DP  - 2006 Oct
TI  - Deregulation of the p16-cyclin D1/cyclin-dependent kinase 4-retinoblastoma 
      pathway involved in the rat bladder carcinogenesis induced by terephthalic 
      acid-calculi.
PG  - 321-8
AB  - Prolonged cell proliferation in response to irritation by calculi may itself 
      evoke malignant transformation of the urothelium. However, the molecular 
      mechanisms underlying this process are still unknown. The aim of the present 
      study was to investigate cell cycle regulatory mechanisms in bladder 
      carcinogenesis induced by bladder calculi. Six-week-old Wistar rats were 
      consecutively fed a diet containing 5% terephthalic acid (TPA), 5% TPA plus 4% 
      sodium bicarbonate (NaHCO(3)), 4% NaHCO(3), or basal diet for 48 weeks. Animals 
      were killed at weeks 12, 24, and 48. Treatment with 5% TPA caused high incidences 
      of bladder calculi, preneoplastic lesions, and neoplastic lesions. 
      Immunohistochemical examination revealed overexpression of cyclin D1, 
      cyclin-dependent kinase 4 (Cdk4), retinoblastoma (Rb), and proliferating cell 
      nuclear antigen (PCNA) in bladder preneoplastic and neoplastic lesions. In 
      contrast, p16 expression was reduced or absent. These results were confirmed by 
      immunoblotting analysis. Quantitation of mRNA by real-time reverse 
      transcription-polymerase chain reaction (RT-PCR) showed a significant increase in 
      cyclin D1 and PCNA mRNA in tumor cells. None of the 16 transitional cell 
      carcinomas (TCCs) had ras mutations as examined by PCR-single strand 
      conformational polymorphism (PCR-SSCP) analysis. These results suggested that 
      deregulation of p16-cyclin D1/Cdk4-Rb pathway, but not oncogenic activation of 
      ras, plays a crucial role in bladder tumorigenesis induced by bladder calculi.
FAU - Cui, Lunbiao
AU  - Cui L
AD  - Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 
      210029, China.
FAU - Shi, Yuan
AU  - Shi Y
FAU - Qian, Jie
AU  - Qian J
FAU - Dai, Guidong
AU  - Dai G
FAU - Wang, Yubang
AU  - Wang Y
FAU - Xia, Yankai
AU  - Xia Y
FAU - Chen, Jianfeng
AU  - Chen J
FAU - Song, Ling
AU  - Song L
FAU - Wang, Shouling
AU  - Wang S
FAU - Wang, Xinru
AU  - Wang X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060729
PL  - Germany
TA  - Urol Res
JT  - Urological research
JID - 0364311
RN  - 0 (Cyclin D)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Cyclins)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Phthalic Acids)
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (RNA, Messenger)
RN  - 0 (Retinoblastoma Protein)
RN  - 6S7NKZ40BQ (terephthalic acid)
SB  - IM
MH  - Animals
MH  - Cell Division
MH  - Cyclin D
MH  - Cyclin-Dependent Kinase Inhibitor p16/*genetics
MH  - Cyclins/*genetics
MH  - Free Radical Scavengers
MH  - Gene Expression Regulation, Neoplastic
MH  - Immunohistochemistry
MH  - Male
MH  - Phthalic Acids
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Proliferating Cell Nuclear Antigen/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Retinoblastoma Protein/*genetics
MH  - Urinary Bladder Neoplasms/etiology/pathology/*physiopathology
MH  - Urinary Calculi/complications/pathology/*physiopathology
MH  - Urothelium/metabolism/pathology
EDAT- 2006/08/10 09:00
MHDA- 2007/01/19 09:00
CRDT- 2006/08/10 09:00
PHST- 2006/03/28 00:00 [received]
PHST- 2006/06/12 00:00 [accepted]
PHST- 2006/08/10 09:00 [pubmed]
PHST- 2007/01/19 09:00 [medline]
PHST- 2006/08/10 09:00 [entrez]
AID - 10.1007/s00240-006-0063-3 [doi]
PST - ppublish
SO  - Urol Res. 2006 Oct;34(5):321-8. doi: 10.1007/s00240-006-0063-3. Epub 2006 Jul 29.