Expression of a human multidrug resistance gene in human ovarian carcinoma cell lines

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Human ovarian adenocarcinoma cell lines were analyzed for mdr 1 gene expression, finding mdr 1 transcripts in only one highly drug-resistant cell line, suggesting its partial role in chemoresistance.

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Abstract

To investigate the possible role of the multidrug resistance phenotype to chemoresistance in human ovarian carcinoma, we have analyzed human multidrug resistance gene (mdr 1) expression in 8 human ovarian adenocarcinoma cell lines. An increase in P-glycoprotein level specific to multidrug-resistant tumor cells was not apparently associated with the increase in resistance to vincristine (VCR) or doxorubicin (Adriamycin). Mdr 1 transcripts (4.5 kilobases) were observed in the RNA preparation obtained from only one cell line (SHIN-3) that showed the highest resistance to both drugs in vitro and in vivo. No cell lines showed mdr 1 DNA amplification. These results suggest that the insensitivity of human ovarian carcinoma to chemotherapy could be partly explained by the expression of mdr 1.
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Summary To investigate the possible role of the multidrug resistance phenotype to chemoresistance in human ovarian carcinoma, we have analyzed human multidrug resistance gene (mdr 1) expression in 8 human ovarian adenocarcinoma cell lines. An increase in P-glycoprotein level specific to multidrug-resistant tumor cells was not apparently associated with the increase in resistance to vincristine (VCR) or doxorubicin (Adriamycin). Mdr 1 transcripts (4.5 kilobases) were observed in the RNA preparation obtained from only one cell line (SHIN-3) that showed the highest resistance to both drugs in vitro and in vivo. No cell lines showed mdr 1 DNA amplification. These results suggest that the insensitivity of human ovarian carcinoma to chemotherapy could be partly explained by the expression of mdr 1. Similar content being viewed by others References Gerlach J, Kartner N, Bell DR, Ling V (1986) Multidrug resistance. Cancer Surv 5:25–46 Gottesman MM, Pastan I (1988) Resistance to multiple chemotherapeutic agents in human cancer cells. TIPS 9:54–58 Tsuruo T (1988) Mechanisms of multidrug resistance and implications for therapy. Jpn J Cancer Res (Gann) 79:285–296 Sekiya S, Tanaka N, Takamizawa H (1990) Production of various marker substances in human ovarian cancer cell lines of epithelial origin. Arch Gynecol Obstet 248:103–110 Hamada H, Tsuruo T (1986) Functional role of the 170- to 180-kDa glycoprotein specific to drugresistant tumor cells as revealed by monoclonal antibodies. Proc Natl Acad Sci USA 83:7758–7789 Shirasawa H, Tomita Y, Sekiya S, Takamizawa H, Shimizu B (1987) Integratiion and transcription of human papillomavirus type 16 and 18 sequences in cell lines derived from cervical carcinomas. J Gen Virol 68:583–591 Sugimoto Y, Tsuruo T (1987) DNA-mediated transfer and cloning of a human multidrug-resistant gene of adriamycin-resistant myelogenous leukemia K 562. Cancer Res 47:2620–2625 Sugimoto Y, Asami N, Tsuruo T (1989) Expression of P-glycoprotein mRNA in human gastric tumors. Jpn J Cancer Res (Gann) 80:993–999 Ishida Y, Ohtsu T, Hamada H, Sugimoto Y, Tobinai K, Minato K, Tsuruo T, Shimoyama M (1989) Multidrug resistance in cultured human leukemia and lymphoma cell lines detected by a monoclonal antibody, MRK 16. Jpn J Cancer Res (Gann) 80:1006–1013 Bell DR, Gerlach JH, Kartner N, Buick RN, Ling V (1985) Detection of P-glycoprotein in ovarian cancer: a molecular marker associated with multidrug resistance. J Clin Oncol 3:311–315 Bourhis J, Goldstein LJ, Riou G, Pastan I, Gottesman MM, Benard J (1989) Expression of a human multidrug gene in ovarian carcinomas. Cancer Res 49:5062–5065 Volm M, Efferth T, Bak M, Mattern J (1989) Detection of drug resistance in human ovarian carcinoma. Arch Gynecol Obstet 244:123–128 Chan HSL, Bradley G, Thorner P, Haddad G, Gallie BL, Ling V (1988) A sensitive method for immunocytochemical detection of P-glycoprotein in multidrug-resistant human ovarian carcinoma cell lines. Lab Invest 59:870–875 Bernard J, Da Silva J, Teyssier J-R, Riou G (1989) Over-expression of mdr 1 gene with no DNA amprification in a multiple-drug-resistant human ovarian carcinoma cell line. Int J Cancer 43:471–477 Bradley G, Naik M, Ling V (1989) P-glycoprotein expression in multi-drug-resistant human ovarian carcinoma cell lines. Cancer Res 49:2790–2796 Author information Authors and Affiliations Rights and permissions About this article Cite this article Sekiya, S., Nunoyama, T., Shirasawa, H. et al. Expression of a human multidrug resistance gene in human ovarian carcinoma cell lines. Arch Gynecol Obstet 251, 79–86 (1992). https://doi.org/10.1007/BF02759915 Received: Accepted: Issue date: DOI: https://doi.org/10.1007/BF02759915

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endometriosis

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Gene Expression Regulation, Neoplastic Membrane Glycoproteins Ovarian Neoplasms Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma ATP Binding Cassette Transporter, Subfamily B, Member 1 Cell Division Cell Division Cell Line Cystadenocarcinoma Cystadenocarcinoma Cystadenocarcinoma Cystadenocarcinoma Doxorubicin Doxorubicin Endometriosis Endometriosis Endometriosis

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