Compounds > n(alpha)-(4-amino-4-deoxy-n(10)--methylpteroyl-n(epsilon)-4--fluoresceinthiocarbamoyl)-l-lysine-trihydrate

n(alpha)-(4-amino-4-deoxy-n(10)--methylpteroyl-n(epsilon)-4--fluoresceinthiocarbamoyl)-l-lysine-trihydrate and Breast-Neoplasms

n(alpha)-(4-amino-4-deoxy-n(10)--methylpteroyl-n(epsilon)-4--fluoresceinthiocarbamoyl)-l-lysine-trihydrate has been researched along with Breast-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for n(alpha)-(4-amino-4-deoxy-n(10)--methylpteroyl-n(epsilon)-4--fluoresceinthiocarbamoyl)-l-lysine-trihydrate and Breast-Neoplasms

Article	Year
Folate transport and the modulation of antifolate sensitivity in a methotrexate-resistant human breast cancer cell line. Cancer communications, 1991, Volume: 3, Issue:12 The mechanism of acquired methotrexate-resistance in an estrogen-receptor positive human breast cancer cell line (MTX(R)ZR-75-1) was studied. MTX(R) ZR-75-1 cells are 250-fold resistant to methotrexate when grown in the presence of 1 microM folinic acid and 2,400-fold resistant in the presence of 1 microM folic acid. This drug resistant cell line also showed collateral sensitivity (10-fold) to trimetrexate (TMQ), when grown in the presence of folinic acid. Using fluoresceinated methotrexate (F-MTX), FACS analysis indicated that there is no intracellular accumulation of methotrexate into MTX(R) ZR-75-1 cells, as determined by competition of F-MTX and methotrexate binding to dihydrofolate reductase. These characteristics strongly indicate that the mechanism of resistance involved down regulation of the reduced-folate transporter. To investigate this further, the transport kinetics of parental and MTX(R) ZR-75-1 cells were examined. Although the V(max) for methotrexate transport in wild-type (WT) ZR-75-1 breast cancer cells was 1-2 orders of magnitude lower than that in the well characterized leukemia cell lines, such as L1210 and CCRF-CEM cells, kinetic analysis indicated that transport of methotrexate into WT ZR-75-1 cells involved a mechanism that was similar if not identical to the reduced folate transporter. In contrast, no specific uptake of methotrexate was detected in MTX(R) ZR-75-1cells. Furthermore, neither cell line expressed detectable levels of folate binding protein, a binding protein with high affinity for folic acid as well as for reduced folates and antifolates. These results indicate that the level of expression of the reduced-folate carrier may be an important factor in determining the sensitivity of breast cancer cells as well as leukemia cells to antifolate compounds. Topics: Animals; Antimetabolites, Antineoplastic; Biological Transport; Breast Neoplasms; Carrier Proteins; Drug Resistance, Neoplasm; Flow Cytometry; Folate Receptors, GPI-Anchored; Folic Acid; Folic Acid Antagonists; Humans; Leucovorin; Leukemia; Methotrexate; Mice; Receptors, Cell Surface; Receptors, Estrogen; Tetrahydrofolate Dehydrogenase; Trimetrexate; Tumor Cells, Cultured; Vitamin B Complex	1991

Article

Year

Folate transport and the modulation of antifolate sensitivity in a methotrexate-resistant human breast cancer cell line.

Cancer communications, 1991, Volume: 3, Issue:12

The mechanism of acquired methotrexate-resistance in an estrogen-receptor positive human breast cancer cell line (MTX(R)ZR-75-1) was studied. MTX(R) ZR-75-1 cells are 250-fold resistant to methotrexate when grown in the presence of 1 microM folinic acid and 2,400-fold resistant in the presence of 1 microM folic acid. This drug resistant cell line also showed collateral sensitivity (10-fold) to trimetrexate (TMQ), when grown in the presence of folinic acid. Using fluoresceinated methotrexate (F-MTX), FACS analysis indicated that there is no intracellular accumulation of methotrexate into MTX(R) ZR-75-1 cells, as determined by competition of F-MTX and methotrexate binding to dihydrofolate reductase. These characteristics strongly indicate that the mechanism of resistance involved down regulation of the reduced-folate transporter. To investigate this further, the transport kinetics of parental and MTX(R) ZR-75-1 cells were examined. Although the V(max) for methotrexate transport in wild-type (WT) ZR-75-1 breast cancer cells was 1-2 orders of magnitude lower than that in the well characterized leukemia cell lines, such as L1210 and CCRF-CEM cells, kinetic analysis indicated that transport of methotrexate into WT ZR-75-1 cells involved a mechanism that was similar if not identical to the reduced folate transporter. In contrast, no specific uptake of methotrexate was detected in MTX(R) ZR-75-1cells. Furthermore, neither cell line expressed detectable levels of folate binding protein, a binding protein with high affinity for folic acid as well as for reduced folates and antifolates. These results indicate that the level of expression of the reduced-folate carrier may be an important factor in determining the sensitivity of breast cancer cells as well as leukemia cells to antifolate compounds.

Topics: Animals; Antimetabolites, Antineoplastic; Biological Transport; Breast Neoplasms; Carrier Proteins; Drug Resistance, Neoplasm; Flow Cytometry; Folate Receptors, GPI-Anchored; Folic Acid; Folic Acid Antagonists; Humans; Leucovorin; Leukemia; Methotrexate; Mice; Receptors, Cell Surface; Receptors, Estrogen; Tetrahydrofolate Dehydrogenase; Trimetrexate; Tumor Cells, Cultured; Vitamin B Complex

1991