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Cell density-dependent regulation of mdr-1 gene expression in murine colon cancer cells

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We studied the regulation of mdr-1 and P-glycoprotein in sparse and confluent cultures of murine CT-26 colon carcinoma cells. The expression level of mdr-1 mRNA transcripts (analyzed by Northern blot and in situ hybridization) and P-glycoprotein (analyzed by flow cytometry) inversely correlated with cell density. The modulation of mdr gene expression in sparse and confluent cells was not related to cell division, nutrient depletion, inhibition of protein synthesis, gap junction status, extracellular ATP, or the presence of various extracellular matrixes, but may be related to cell-density and cell-contact mediated changes in phosphatase activity. The confluence-mediated downmodulation of mdr-1 increased the chemosensitivity of the cells to several anticancer drugs commonly associated with an in vitro MDR phenotype by increasing the intracellular accumulation of the drugs. These data may explain some of the discrepancies in results obtained when analyzing mdr gene expression in tumors growing in vivo or in vitro, and why mdi expression in tumors is localized to the periphery of the lesions.
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Document Type: Research Article

Affiliations: UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CELL BIOL,HOUSTON,TX 77030.

Publication date: November 1, 1996

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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