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Titolo:
MDR1 gene overexpression and altered degree of methylation at the promoterregion in bladder cancer during chemotherapeutic treatment
Autore:
Tada, Y; Wada, M; Kuroiwa, K; Kinugawa, N; Harada, T; Nagayama, J; Nakagawa, M; Naito, S; Kuwano, M;
Indirizzi:
Kyushu Univ, Grad Sch Med Sci, Dept Med Biochem, Higashi Ku, Fukuoka 8128582, Japan Kyushu Univ Fukuoka Japan 8128582 em, Higashi Ku, Fukuoka 8128582, Japan Kyushu Univ, Grad Sch Med Sci, Dept Urol, Higashi Ku, Fukuoka 8128582, Japan Kyushu Univ Fukuoka Japan 8128582 ol, Higashi Ku, Fukuoka 8128582, Japan Kyushu Univ, Grad Sch Med Sci, Dept Med Informat, Higashi Ku, Fukuoka 8128582, Japan Kyushu Univ Fukuoka Japan 8128582 at, Higashi Ku, Fukuoka 8128582, Japan Kagoshima Univ, Fac Med, Dept Urol, Kagoshima 8908520, Japan Kagoshima Univ Kagoshima Japan 8908520 pt Urol, Kagoshima 8908520, Japan
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 12, volume: 6, anno: 2000,
pagine: 4618 - 4627
SICI:
1078-0432(200012)6:12<4618:MGOAAD>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
RESISTANCE-ASSOCIATED PROTEIN; POLYMERASE CHAIN-REACTION; MULTIPLE-DRUG RESISTANCE; MULTIDRUG-RESISTANCE; CELL-LINES; P-GLYCOPROTEIN; NUCLEAR EXPRESSION; BINDING-PROTEIN; DNA METHYLATION; CPG ISLANDS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Wada, M Kyushu Univ, Grad Sch Med Sci, Dept Med Biochem, Higashi Ku, 3-1-1Maidashi, Fukuoka 8128582, Japan Kyushu Univ 3-1-1 Maidashi Fukuoka Japan8128582 a 8128582, Japan
Citazione:
Y. Tada et al., "MDR1 gene overexpression and altered degree of methylation at the promoterregion in bladder cancer during chemotherapeutic treatment", CLIN CANC R, 6(12), 2000, pp. 4618-4627

Abstract

Overexpression of the multidrug resistance I (MDR1) gene is closely associated with the clinical outcome of hematopoietic malignancies, but the alteration of its expression during chemotherapeutic treatment and the precise mechanism underlying MDR1 gene overexpression in solid tumors remains unclear. We determined the expression and degree of methylation at the promoter of the MDR1 gene in bladder cancer, The mRNA levels of the MDR1 gene were found to be markedly enhanced, 3.5- to 5.7-fold higher in bladder cancers after chemotherapeutic treatment than those in untreated primary tumors. The MDR1 gene was overexpressed in recurrent tumors in 89% of patients who showed rerecurrence, whereas overexpression was observed in 25% of the patients without re-recurrence. A statistically significant inverse correlation existed between MDR1 expression and the methylation of 5'CpG sites at the promoter in patients with bladder cancer after chemotherapeutic treatment, with the degree of methylation at several CpG sites, rather than other specific sites, involved in this regulation. Consistent with the increase in MDR1 expression, the frequency of patients with a hypermethylated promoter decreased to 50 and 17% after intravesical and systemic chemotherapy, respectively. Thus, overexpression of the MDR1 gene might be a prognostic marker for intravesical recurrence, whereas methylation of the promoter region negatively regulates MDR1 expression and the appearance of multidrug resistance mediated by beta -glycoprotein in bladder cancers.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/04/20 alle ore 22:52:25