Aran, J M, Gottesman, M M, Pastan, I
Bicistronic cassettes under control of a single promoter have recently been suggested as useful tools for coordinate expression of two different foreign proteins in mammalian cells. Using the long 5'...
Gosse, M E, Padmanabhan, A, Fleischmann, R D, Gottesman, M M
The regulatory and catalytic subunits of cAMP-dependent protein kinase (PKA) were coexpressed within the same bacterial cell using a polycistronic bacterial T7 expression vector encoding Chinese...
A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease.
Wang, N, Gottesman, S, Willingham, M C, Gottesman, M M, Maurizi, M R
We have cloned a human ATP-dependent protease that is highly homologous to members of the bacterial Lon protease family. The cloned gene encodes a protein of 963 amino acids with a calculated...
Ambudkar, S V, Lelong, I H, Zhang, J, Cardarelli, C O, Gottesman, M M, Pastan, I
Multidrug-resistant human tumor cells overexpress the MDR1 gene product P-glycoprotein, which is believed to function as an ATP-dependent efflux pump. In this study we demonstrate that the partially...
Mickisch, G H, Merlino, G T, Galski, H, Gottesman, M M, Pastan, I
The development of preclinical models for the rapid testing of agents that circumvent multidrug resistance in cancer is a high priority of research on drug resistance. A common form of multidrug...
Pfützner, W., Terunuma, A., Tock, C. L., Snead, E. K., Kolodka, T. M., Gottesman, M. M., ...
For skin gene therapy, achieving prolonged high-level gene expression in a significant percentage of keratinocytes (KC) is difficult because we cannot selectively target KC stem cells. We now...
Schoenlein, P V, Shen, D W, Barrett, J T, Pastan, I, Gottesman, M M
This study characterizes amplified structures carrying the human multidrug resistance (MDR) genes in colchicine-selected multidrug resistant KB cell lines and strongly supports a model of gene...
Ramachandra, M, Ambudkar, S V, Gottesman, M M, Pastan, I, Hrycyna, C A
Human P-glycoprotein (Pgp) is a 170-kDa plasma membrane protein that confers multidrug resistance to otherwise sensitive cells. A mutation in Pgp, G185-->V, originally identified as a spontaneous...
ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells.
Horio, M, Gottesman, M M, Pastan, I
Resistance of human cancer cells to multiple cytotoxic hydrophobic agents (multidrug resistance) is due to overexpression of the "MDR1" gene, whose product is the plasma membrane P-glycoprotein....
Pastan, I, Gottesman, M M, Ueda, K, Lovelace, E, Rutherford, A V, Willingham, M C
A full-length cDNA for the human multidrug resistance gene 1 (MDR1) has been inserted into a retroviral vector containing a murine Harvey sarcoma virus from which the viral oncogene was deleted....
Thiebaut, F, Tsuruo, T, Hamada, H, Gottesman, M M, Pastan, I, Willingham, M C
Monoclonal antibody MRK16 was used to determine the location of P-glycoprotein, the product of the multidrug-resistance gene (MDR1), in normal human tissues. The protein was found to be concentrated...
Expression of a multidrug-resistance gene in human tumors and tissues.
Fojo, A T, Ueda, K, Slamon, D J, Poplack, D G, Gottesman, M M, Pastan, I
The identification and cloning of a segment of a human multidrug resistance gene (mdr1) was reported recently. To examine the molecular basis of one type of multidrug resistance, we have prepared RNA...
Ueda, K, Cardarelli, C, Gottesman, M M, Pastan, I
Intrinsic and acquired multidrug resistance (MDR) is an important problem in cancer therapy. MDR in human KB carcinoma cells selected for resistance to colchicine, vinblastine, or doxorubicin (former...
A monoclonal antibody-Pseudomonas toxin conjugate that specifically kills multidrug-resistant cells.
FitzGerald, D J, Willingham, M C, Cardarelli, C O, Hamada, H, Tsuruo, T, Gottesman, M M, ...
One form of multidrug resistance is due to the expression of a 170-kDa energy-dependent drug efflux pump called P-glycoprotein in the plasma membranes of human cancer cells. We have prepared...
Steinert, P M, Idler, W W, Cabral, F, Gottesman, M M, Goldman, R D
This paper presents evidence that the intermediate filament (IF) subunits of muscle cells (skeletin or desmin) and fibroblastic cells (decamin or vimentin) separately form homopolymer IF in vitro...
Cabral, F, Abraham, I, Gottesman, M M
Taxol is a plant alkaloid that has antimitotic activity and appears to stabilize microtubules [Schiff, P. B., Fant, J. & Horwitz, S. B. (1979) Nature (London) 277, 665-667]. Taxol-resistant cells...
Rabin, M S, Doherty, P J, Gottesman, M M
Treatment of mouse NIH 3T3 cells with the phorbol ester tumor promoter, phorbol 12-myristate 13-acetate, results in altered transcription of several genes as measured in nuclear run-off experiments....
Cornwell, M M, Safa, A R, Felsted, R L, Gottesman, M M, Pastan, I
Multiple drug resistance of tumor cells is a common problem in cancer therapy. We have demonstrated that membrane vesicles from highly multidrug-resistant human KB carcinoma cell lines exhibit...
Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells.
Roninson, I B, Chin, J E, Choi, K G, Gros, P, Housman, D E, Fojo, A, ...
The ability of tumor cells to develop simultaneous resistance to structurally different cytotoxic drugs constitutes a major problem in cancer chemotherapy. It was previously demonstrated that...
A polymorphic HindIII site within the human multidrug resistance gene 1 (MDR1).
Yoshimoto, K, Iwahana, H, Yokogoshi, Y, Saito, S, Shiraishi, M, Sekiya, T, ...
Galski, H, Sullivan, M, Willingham, M C, Chin, K V, Gottesman, M M, Pastan, I, ...
The human multidrug resistance gene (MDR1) encodes a drug efflux pump glycoprotein (P-glycoprotein) responsible for resistance to multiple cytotoxic drugs. A plasmid carrying a human MDR1 cDNA under...
Kane, S E, Troen, B R, Gal, S, Ueda, K, Pastan, I, Gottesman, M M
Malignantly transformed mouse fibroblasts synthesize and secrete large amounts of major excreted protein (MEP), a 39,000-dalton precursor to an acid protease (cathepsin L). To evaluate the possible...
Doherty, P J, Hua, L, Liau, G, Gal, S, Graham, D E, Sobel, M, ...
The major excreted protein of transformed mouse fibroblasts, a secreted, mannose 6-phosphate-containing glycoprotein, is induced in nontransformed cells by a variety of transforming agents, by...
Frick, K K, Doherty, P J, Gottesman, M M, Scher, C D
Platelet-derived growth factor (PDGF) stimulates density-arrested BALB/c-3T3 cells to synthesize MEP, a lysosomal protein. This enhanced synthesis appears to be largely regulated by the...
Multidrug resistance of DNA-mediated transformants is linked to transfer of the human mdr1 gene.
Shen, D W, Fojo, A, Roninson, I B, Chin, J E, Soffir, R, Pastan, I, ...
Mouse NIH 3T3 cells were transformed to multidrug resistance with high-molecular-weight DNA from multidrug-resistant human KB carcinoma cells. The patterns of cross resistance to colchicine,...
Whitfield, C, Abraham, I, Ascherman, D, Gottesman, M M
Total genomic DNA from a temperature-sensitive, colcemid-resistant Chinese hamster ovary (CHO) cell mutant expressing an electrophoretic variant beta-tubulin was used to transform wild-type CHO cells...
Cyclic AMP-dependent protein kinase regulates sensitivity of cells to multiple drugs.
Abraham, I, Hunter, R J, Sampson, K E, Smith, S, Gottesman, M M, Mayo, J K
The isolation of mutant cell lines affecting the activity of cyclic AMP (cAMP)-dependent protein kinase (PK-A) has made it possible to determine the function of this kinase in mammalian cells. We...
Cholera toxin treatment stimulates tumorigenicity of Rous sarcoma virus-transformed cells.
Gottesman, M M, Roth, C, Vlahakis, G, Pastan, I
Chinese hamster ovary cells transformed by Rous sarcoma virus form tumors poorly in nude mice. Tumorigenicity was markedly stimulated by pretreatment of the cells with cholera toxin, which raises...
2,4-Dichlorobenzyl thiocyanate, an antimitotic agent that alters microtubule morphology.
Abraham, I, Dion, R L, Chi, D M, Gottesman, M M, Hamel, E
A compound of simple structure, 2,4-dichlorobenzyl thiocyanate (DCBT), is an antimitotic agent with a number of unusual properties. The drug causes an extreme reorganization of microtubules in cells...
Acquisition of a determinant for chloramphenicol resistance by coliphage lambda.
A determinanat for chloramphenicol resistance, cam, initially detected on a resistance transfer factor (RTF) and since transferred to phage P1, may be acquired from P1 by coliphage lambda. Lambdapcam...
Amplification of DNA sequences in human multidrug-resistant KB carcinoma cells.
Fojo, A T, Whang-Peng, J, Gottesman, M M, Pastan, I
Four KB carcinoma cell lines selected independently for resistance to either colchicine, adriamycin, or vinblastine were studied. All cell lines showed high levels of resistance to the selecting drug...
Transformation-dependent secretion of a low molecular weight protein by murine fibroblasts.
A protocol has been devised to radiolabel proteins secreted by murine fibroblasts in vitro. A radiolabeled polypeptide of molecular weight 35,000 is released into medium in relatively large amounts...
Richert, N, Akiyama, S, Shen, D, Gottesman, M M, Pastan, I
Human KB carcinoma cells were selected in sequential steps for resistance to colchicine and found to be cross-resistant to multiple drugs, including vinblastine, adriamycin, and actinomycin D....
Smith, S M, Kane, S E, Gal, S, Mason, R W, Gottesman, M M
Cathepsin L is a major lysosomal cysteine proteinase in mouse and human cells. Despite similar predicted molecular masses, procathepsin L in these two species migrates on SDS/polyacrylamide gels with...
Gosse, M E, Fleischmann, R, Marshall, M, Wang, N, Garges, S, Gottesman, M M
The type-I regulatory subunit (RI) of the cyclic AMP-dependent protein kinase (PKA) from Chinese hamster ovary (CHO) cells has been cloned and expressed in a strain of BL21(DE3) Escherichia coli...
Troen, B R, Gal, S, Gottesman, M M
The major excreted protein (MEP) of malignantly transformed mouse fibroblasts is a secreted thiol proteinase. Sequencing of the MEP cDNA shows the coding region for the protein to be identical with...
Mason, R W, Gal, S, Gottesman, M M
The major excreted protein (MEP) purified from Kirsten-virus-transformed 3T3 fibroblasts and mature human cathepsin L were compared in respect to a number of catalytic criteria and found to be...
Isolation and sequence of a cDNA for human pro-(cathepsin L).
The major excreted protein (MEP) of malignantly transformed mouse fibroblasts is the precursor to an acid proteinase with enzymic specificity similar to that of human cathepsin L. By...
The lysosomal cysteine proteinase cathepsin L is synthesized in cultured mouse NIH 3T3 cells as a 39 kDa precursor and processed intracellularly into active 29 kDa and 20 kDa + 5 kDa lysosomal forms....
Aran, J M, Gottesman, M M, Pastan, I
Bicistronic cassettes under control of a single promoter have recently been suggested as useful tools for coordinate expression of two different foreign proteins in mammalian cells. Using the long 5'...
Gosse, M E, Padmanabhan, A, Fleischmann, R D, Gottesman, M M
The regulatory and catalytic subunits of cAMP-dependent protein kinase (PKA) were coexpressed within the same bacterial cell using a polycistronic bacterial T7 expression vector encoding Chinese...
A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease.
Wang, N, Gottesman, S, Willingham, M C, Gottesman, M M, Maurizi, M R
We have cloned a human ATP-dependent protease that is highly homologous to members of the bacterial Lon protease family. The cloned gene encodes a protein of 963 amino acids with a calculated...
Ambudkar, S V, Lelong, I H, Zhang, J, Cardarelli, C O, Gottesman, M M, Pastan, I
Multidrug-resistant human tumor cells overexpress the MDR1 gene product P-glycoprotein, which is believed to function as an ATP-dependent efflux pump. In this study we demonstrate that the partially...
Mickisch, G H, Merlino, G T, Galski, H, Gottesman, M M, Pastan, I
The development of preclinical models for the rapid testing of agents that circumvent multidrug resistance in cancer is a high priority of research on drug resistance. A common form of multidrug...
Pfützner, W., Terunuma, A., Tock, C. L., Snead, E. K., Kolodka, T. M., Gottesman, M. M., ...
For skin gene therapy, achieving prolonged high-level gene expression in a significant percentage of keratinocytes (KC) is difficult because we cannot selectively target KC stem cells. We now...
Schoenlein, P V, Shen, D W, Barrett, J T, Pastan, I, Gottesman, M M
This study characterizes amplified structures carrying the human multidrug resistance (MDR) genes in colchicine-selected multidrug resistant KB cell lines and strongly supports a model of gene...
Ramachandra, M, Ambudkar, S V, Gottesman, M M, Pastan, I, Hrycyna, C A
Human P-glycoprotein (Pgp) is a 170-kDa plasma membrane protein that confers multidrug resistance to otherwise sensitive cells. A mutation in Pgp, G185-->V, originally identified as a spontaneous...
ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells.
Horio, M, Gottesman, M M, Pastan, I
Resistance of human cancer cells to multiple cytotoxic hydrophobic agents (multidrug resistance) is due to overexpression of the "MDR1" gene, whose product is the plasma membrane P-glycoprotein....
Pastan, I, Gottesman, M M, Ueda, K, Lovelace, E, Rutherford, A V, Willingham, M C
A full-length cDNA for the human multidrug resistance gene 1 (MDR1) has been inserted into a retroviral vector containing a murine Harvey sarcoma virus from which the viral oncogene was deleted....
Thiebaut, F, Tsuruo, T, Hamada, H, Gottesman, M M, Pastan, I, Willingham, M C
Monoclonal antibody MRK16 was used to determine the location of P-glycoprotein, the product of the multidrug-resistance gene (MDR1), in normal human tissues. The protein was found to be concentrated...
Expression of a multidrug-resistance gene in human tumors and tissues.
Fojo, A T, Ueda, K, Slamon, D J, Poplack, D G, Gottesman, M M, Pastan, I
The identification and cloning of a segment of a human multidrug resistance gene (mdr1) was reported recently. To examine the molecular basis of one type of multidrug resistance, we have prepared RNA...
Ueda, K, Cardarelli, C, Gottesman, M M, Pastan, I
Intrinsic and acquired multidrug resistance (MDR) is an important problem in cancer therapy. MDR in human KB carcinoma cells selected for resistance to colchicine, vinblastine, or doxorubicin (former...
A monoclonal antibody-Pseudomonas toxin conjugate that specifically kills multidrug-resistant cells.
FitzGerald, D J, Willingham, M C, Cardarelli, C O, Hamada, H, Tsuruo, T, Gottesman, M M, ...
One form of multidrug resistance is due to the expression of a 170-kDa energy-dependent drug efflux pump called P-glycoprotein in the plasma membranes of human cancer cells. We have prepared...
Steinert, P M, Idler, W W, Cabral, F, Gottesman, M M, Goldman, R D
This paper presents evidence that the intermediate filament (IF) subunits of muscle cells (skeletin or desmin) and fibroblastic cells (decamin or vimentin) separately form homopolymer IF in vitro...
Cabral, F, Abraham, I, Gottesman, M M
Taxol is a plant alkaloid that has antimitotic activity and appears to stabilize microtubules [Schiff, P. B., Fant, J. & Horwitz, S. B. (1979) Nature (London) 277, 665-667]. Taxol-resistant cells...
Rabin, M S, Doherty, P J, Gottesman, M M
Treatment of mouse NIH 3T3 cells with the phorbol ester tumor promoter, phorbol 12-myristate 13-acetate, results in altered transcription of several genes as measured in nuclear run-off experiments....
Cornwell, M M, Safa, A R, Felsted, R L, Gottesman, M M, Pastan, I
Multiple drug resistance of tumor cells is a common problem in cancer therapy. We have demonstrated that membrane vesicles from highly multidrug-resistant human KB carcinoma cell lines exhibit...
Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells.
Roninson, I B, Chin, J E, Choi, K G, Gros, P, Housman, D E, Fojo, A, ...
The ability of tumor cells to develop simultaneous resistance to structurally different cytotoxic drugs constitutes a major problem in cancer chemotherapy. It was previously demonstrated that...
A polymorphic HindIII site within the human multidrug resistance gene 1 (MDR1).
Yoshimoto, K, Iwahana, H, Yokogoshi, Y, Saito, S, Shiraishi, M, Sekiya, T, ...
Galski, H, Sullivan, M, Willingham, M C, Chin, K V, Gottesman, M M, Pastan, I, ...
The human multidrug resistance gene (MDR1) encodes a drug efflux pump glycoprotein (P-glycoprotein) responsible for resistance to multiple cytotoxic drugs. A plasmid carrying a human MDR1 cDNA under...
Kane, S E, Troen, B R, Gal, S, Ueda, K, Pastan, I, Gottesman, M M
Malignantly transformed mouse fibroblasts synthesize and secrete large amounts of major excreted protein (MEP), a 39,000-dalton precursor to an acid protease (cathepsin L). To evaluate the possible...
Doherty, P J, Hua, L, Liau, G, Gal, S, Graham, D E, Sobel, M, ...
The major excreted protein of transformed mouse fibroblasts, a secreted, mannose 6-phosphate-containing glycoprotein, is induced in nontransformed cells by a variety of transforming agents, by...
Frick, K K, Doherty, P J, Gottesman, M M, Scher, C D
Platelet-derived growth factor (PDGF) stimulates density-arrested BALB/c-3T3 cells to synthesize MEP, a lysosomal protein. This enhanced synthesis appears to be largely regulated by the...
Multidrug resistance of DNA-mediated transformants is linked to transfer of the human mdr1 gene.
Shen, D W, Fojo, A, Roninson, I B, Chin, J E, Soffir, R, Pastan, I, ...
Mouse NIH 3T3 cells were transformed to multidrug resistance with high-molecular-weight DNA from multidrug-resistant human KB carcinoma cells. The patterns of cross resistance to colchicine,...
Whitfield, C, Abraham, I, Ascherman, D, Gottesman, M M
Total genomic DNA from a temperature-sensitive, colcemid-resistant Chinese hamster ovary (CHO) cell mutant expressing an electrophoretic variant beta-tubulin was used to transform wild-type CHO cells...