PMID- 14522917 OWN - NLM STAT- MEDLINE DCOM- 20031204 LR - 20211203 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 63 IP - 18 DP - 2003 Sep 15 TI - Mislocalization of membrane proteins associated with multidrug resistance in cisplatin-resistant cancer cell lines. PG - 5909-16 AB - The accumulation of [(14)C]carboplatin and [(3)H]methotrexate is reduced in single-step KB epidermoid adenocarcinoma (KB-CP) cells, which are cross-resistant to carboplatin, methotrexate, and sodium arsenite. In these KB-CP cells, multidrug resistance is accompanied by mislocalization of multidrug resistance associated protein (MRP) 1 and other membrane proteins such as folate-binding protein. MRP1 was not decreased in amount in single-step variants but accumulates in a cytoplasmic fraction, and its apparent molecular weight was altered probably because of reduced glycosylation in resistant cells. This low-density compartment was partially labeled with antibodies to lectin-GSII (a Golgi marker) and Bip/GRP78 (an endoplasmic reticulum marker). Pulse-chase labeling of MRP1 with (35)S-methionine and (35)S-cysteine and pulse-chase biotinylation of cell surface MRP1 suggests that membrane protein mislocalization is caused mainly by a defect of plasma membrane protein recycling, manifested also as a defect in acidification of lysosomes. The reduced accumulation of cytotoxic compounds in the KB-CP cells is presumed to result from the failure of carrier proteins and/or transporters to localize to the plasma membrane. FAU - Liang, Xing-Jie AU - Liang XJ AD - Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4254, USA. FAU - Shen, Ding-Wu AU - Shen DW FAU - Garfield, Susan AU - Garfield S FAU - Gottesman, Michael M AU - Gottesman MM LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) RN - 0 (Antineoplastic Agents) RN - 0 (Carbon Radioisotopes) RN - 0 (Carrier Proteins) RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (Folate Receptors, GPI-Anchored) RN - 0 (HSPA5 protein, human) RN - 0 (Receptors, Cell Surface) RN - 0 (Succinimides) RN - 0 (Sulfur Radioisotopes) RN - 0 (Triiodobenzoic Acids) RN - 0 (sulfo-N-hydroxysuccinimide-biotin) RN - 10028-17-8 (Tritium) RN - 6SO6U10H04 (Biotin) RN - AE28F7PNPL (Methionine) RN - BG3F62OND5 (Carboplatin) RN - HW8W27HTXX (iodixanol) RN - K848JZ4886 (Cysteine) RN - Q20Q21Q62J (Cisplatin) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism MH - Antineoplastic Agents/pharmacokinetics/*pharmacology MH - Biotin/*analogs & derivatives/metabolism MH - Carbon Radioisotopes MH - Carboplatin/pharmacokinetics MH - Carrier Proteins/*metabolism MH - Cell Membrane/metabolism MH - Cisplatin/pharmacokinetics/*pharmacology MH - Cysteine/metabolism MH - Drug Resistance, Multiple/*physiology MH - Drug Resistance, Neoplasm MH - Endoplasmic Reticulum Chaperone BiP MH - Folate Receptors, GPI-Anchored MH - HeLa Cells MH - Humans MH - KB Cells MH - Lysosomes/metabolism MH - Methionine/metabolism MH - Methotrexate/pharmacokinetics MH - *Receptors, Cell Surface MH - Succinimides/metabolism MH - Sulfur Radioisotopes MH - Triiodobenzoic Acids/chemistry MH - Tritium EDAT- 2003/10/03 05:00 MHDA- 2003/12/05 05:00 CRDT- 2003/10/03 05:00 PHST- 2003/10/03 05:00 [pubmed] PHST- 2003/12/05 05:00 [medline] PHST- 2003/10/03 05:00 [entrez] PST - ppublish SO - Cancer Res. 2003 Sep 15;63(18):5909-16.