Methylation-dependent Silencing of the Reduced Folate Carrier Gene in Inherently Methotrexate-resistant Human Breast Cancer Cells

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15 صفحه اول

Silencing of rhomboid domain containing 1 to inhibit the metastasis of human breast cancer cells in vitro

Objective(s): A growing body of evidence indicates that rhomboid domain containing 1 (RHBDD1) plays an important role in a variety of physiological and pathological processes, including tumorigenesis. We aimed to determine the function of RHBDD1 in breast cancer cells. Materials and Methods: In this study, we used the Oncomine™ database to determine the expression patterns of RHBDD1 in normal a...

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Dihydrofolate reductase gene amplification and possible rearrangement in estrogen-responsive methotrexate-resistant human breast cancer cells.

Methotrexate-resistant (MTXR) human breast cancer cells have been obtained which are 1000-fold less sensitive to this drug than the wild type MCF-7 cells from which they were derived. The resistant cells contain approximately a 25-fold increase in the activity of the target enzyme dihydrofolate (DHF) reductase. Enzyme inhibition studies and methotrexate affinity studies fail to reveal any diffe...

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Analysis of dihydrofolate reductase and reduced folate carrier gene status in relation to methotrexate resistance in osteosarcoma cells.

BACKGROUND To evaluate the impact of dihydrofolate reductase (DHFR) and reduced folate carrier (RFC) genes on methotrexate (MTX) resistance in osteosarcoma cells in relation to retinoblastoma (RB1) gene status. MATERIALS AND METHODS A series of human osteosarcoma cell lines-either sensitive or resistant to MTX-and 16 osteosarcoma tumour samples were used in this study. RESULTS In U-2OS MTX-...

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A prominent low-pH methotrexate transport activity in human solid tumors: contribution to the preservation of methotrexate pharmacologic activity in HeLa cells lacking the reduced folate carrier.

Whereas the major folate transporter, the reduced folate carrier (RFC), has a physiological pH optimum, transport activities for folates and antifolates have been detected with low pH optima. Because the interstitial pH in solid tumors is generally acidic, the mechanisms by which antifolates are transported at low pH could be an important determinant of drug activity under these conditions. The...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2001

ISSN: 0021-9258

DOI: 10.1074/jbc.m103181200