Aberrant expression of p27(Kip1) is associated with malignant transformation of the rat urinary bladder epithelium

Citation
K. Ogawa et al., Aberrant expression of p27(Kip1) is associated with malignant transformation of the rat urinary bladder epithelium, CARCINOGENE, 21(1), 2000, pp. 117-121
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
0143-3334 → ACNP
Volume
21
Issue
1
Year of publication
2000
Pages
117 - 121
Database
ISI
SICI code
0143-3334(200001)21:1<117:AEOPIA>2.0.ZU;2-N
Abstract
Alteration in cell cycle regulators is considered to play an important role in carcinogenesis. In order to cast light on changes in reversible hyperpl astic and irreversible tumorigenic lesions in the rat urinary bladder, expr ession of p27(Kip1), cyclin D1 and cyclin E proteins was sequentially compa red. In the first study, 3% uracil was fed for 4 weeks to cause urinary cal culi and consequent hyperplasia and papillomatosis, both regressing after w ithdrawal of the insult. Compared with normal bladder epithelium, in papill omatosis at week 4, the BrdU index and immunohistochemical positivities for cyclin D1 and cyclin E were significantly elevated, whereas values for p27 (Kip1) tended to be reduced. One week after withdrawal of uracil, the BrdU index and positivities for cyclin D1 and cyclin E were decreased to below t he control levels, while positivity for p27(Kip1) was dramatically increase d, with a strong staining intensity. In a second study, rats were initiated with a bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine for 4 wee ks, then fed 3% uracil for 8 weeks. During this latter period, expression o f cyclin D1, cyclin E and p27(Kip1) in hyperplastic urothelium were compara ble with those in the first study. One week after withdrawal of uracil, mos t urothelial lesions regressed, showing high p27(Kip1) and low cyclin D1 an d cyclin E staining. Two weeks after uracil withdrawal, transitional cell c arcinomas, with a low p27(Kip1) and high cyclin D1 and cyclin E staining pa ttern, could be easily distinguished from surrounding regressing epithelium . These data indicate that during regression of papillomatosis after cessat ion of a proliferative stimulus, expression of p27(Kip1) is elevated, accom panied by a lowering of cyclin D1 and cyclin E. In irreversible tumorous bl adder lesions, on the other hand, persistent low expression of p27(Kip1) an d elevated cyclin D1 and cyclin E are characteristic.