Expression of MDR-1 Gene in Transitional Cell Carcinoma and its Correlation with Chemotherapy Response
- 1 July 1996
- journal article
- Published by Wolters Kluwer Health in Journal of Urology
- Vol. 156 (1), 271-275
- https://doi.org/10.1016/s0022-5347(01)66015-4
Abstract
Expression of the mdr-1 gene has been correlated with the chemoresistance mechanisms of some cancer models. In the present study, we tried to evaluate mdr-1 gene expression in transitional cell carcinoma (TCC) in both cultured cells and clinical tumors. The expression status of mdr-1 was further correlated with the response to chemotherapy in both systemic and intravesical models. We evaluated mdr-1 expression levels by reverse transcription polymerase chain reaction and Southern blotting (RT-PCR-SB) and the activity of P-glycoprotein (P-gp) by flow cytometric rhodamine-123 retention and efflux study in 10 TCC cell lines, 2 doxorubicin-resistant sublines (RLs), T24/A and NTUB1/A, and 2 cisplatin-RLs, T24/P and NTUB1/P. Eighty-eight clinical tumors with their benign counterparts were also assayed by RT-PCR-SB to determine mdr-1 expression status. Of the 88 TCC cases, 28 were treated with systemic and 60 with intravesical chemotherapy. Response to chemotherapy in either form was correlated with mdr-1 expression status. By RT-PCR-SB, mdr-1 expression signals were observed in only 2 of the 10 TCC cell lines; only 1 of these had a strong signal and active P-gp function. The other, bearing a weak signal, was negative for active P-gp function. All of the 4 RLs studied showed elevated mdr-1 transcript levels as compared with their mdr-1 negative parental cell lines. Doxorubicin-RLs showed much stronger expression signals than cisplatin-RLs. Active P-gp functions were observed in the 2 doxorubicin-RLs but not in the 2 cisplatin-RLs. The efflux of rhodamine-123 in cells with active P-gp function can be significantly inhibited by 10 micromolar. verapamil. Of the 88 clinical tumors, 62 (70.5 percent) were positive and 26 (29.5 percent)were negative for mdr-1 expression by RT-PCR-SB. All benign counterparts of the 88 tumors were positive for mdr-1 expression. However, no differences in chemotherapy responses were found between the positive and negative mdr-1 expression groups in either systemic chemotherapy (p = 0.32, one-tailed Fisher's exact test) or intravesical chemotherapy (p = 0.52, Cox-Mantel log rank test). Expression of mdr-1 was not commonly seen in TCC cell lines but can be significantly induced by chronic exposure to doxorubicin. Benign transitional cell epithelia seemed to universally express the mdr-1 gene. However, clinical TCCs lost mdr-1 transcript expressions in about 30 percent of cases. Most important, it appeared that mdr-1 expression status did not correlate with the response to chemotherapy in either systemic or intravesical models.Keywords
This publication has 16 references indexed in Scilit:
- DNA ploidy and p-glycoprotein expression as predictive factors of response to neoadjuvant chemotherapy for invasive bladder cancerUrology, 1994
- P-Glycoprotein Expression in Bladder CancerJournal of Urology, 1994
- Establishment and Characterization of Doxorubicin-Resistant Human Bladder Cancer Cell Line, Kk47/admJournal of Urology, 1992
- Intravesical instillation of Adriamycin in the presence or absence of verapamil for the treatment of superficial bladder cancer: preliminary report of a collaborative studyCancer Chemotherapy and Pharmacology, 1992
- Correlation between the Expression of P-Glycoprotein and Multidrug-Resistant Phenotype in Transitional Cell Carcinoma of the Urinary TractEuropean Urology, 1992
- P-glycoproteins in pathology: The multidrug resistance gene family in humansHuman Pathology, 1990
- Multidrug Resistance: Molecular Biology Clinical RelevanceJNCI Journal of the National Cancer Institute, 1989
- Establishment and characterization of a human urinary bladder carcinoma cell line (TSGH‐8301)Journal of Surgical Oncology, 1988
- Multiple-Drug Resistance in Human CancerNew England Journal of Medicine, 1987
- A retrospective study on malignant neoplasms of bladder, lung and liver in blackfoot disease endemic area in TaiwanBritish Journal of Cancer, 1986