Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A membrane protein recognized by monoclonal antibody SQM1 was identified in human squamous carcinomas, including those originating in the head and neck (SqCHN), lung and cervix. Cell lines derived from SqCHN of previously untreated patients expressed high amounts of this protein. In contrast, many cell lines established from SqCHN of patients previously treated with chemotherapy and/or radiation showed diminished amounts of this SQM1 protein. The expression of SQM1 antigen was determined in several SqCHN cell lines made resistant by exposure to methotrexate (MTX) in vitro. The parent cell lines all exhibited strong binding to SQM1 antibody. The MTX-resistant sublines showed much lower membrane binding of SQM1. The lowest SQM1 reactivity was found in cell lines with high resistance to MTX and with diminished rate of MTX transport. Some highly MTX-resistant cell lines which had high levels of dihydrofolate reductase, but which retained a high rate of MTX transport, also retained high levels of SQM1 binding. Reduced SQM1 protein was also found in SqCHN cells which developed resistance to the alkylating drug cis-latinum (CDDP) and which showed reduced membrane transport of CDDP. Cell growth kinetics and non-specific antigenic shifts were not responsible for the differences in SQM1 binding between the parent cell lines and their drug-resistant sublines. The finding of a novel protein which is reduced in cells resistant to MTX and CDDP could contribute to our understanding of the basic mechanisms of drug resistance. By detecting SQM1 protein in clinical specimens, it may be possible to monitor the development of drug resistance in tumors.
 ...
PMID:Reduced membrane protein associated with resistance of human squamous carcinoma cells to methotrexate and cis-platinum. 219 18

Expression of SQM1 protein, a membrane protein, was shown to be reduced in human squamous carcinoma of the head and neck (SqCHN) cell lines made less sensitive to methotrexate (MTX). High correlation of SQM1 protein expression with MTX transport (r = .94) and MTX sensitivity (r = .94) was found in MTX-resistant sublines developed from a clonally drived SqCHN cell line, SCC 15S1. Unlike SQM1 protein, there was no significant difference in amount or molecular weight of reduced-folate binding protein found in the membrane of a MTX-resistant subline, SCC15R1-3 and SCC15S1. Furthermore, MTX surface membrane binding was not significantly altered in SCC15R1-3. Compared to SCC15S1 parent cell line, SCC15R1-3 subline with similar DHFR enzyme level and MTX polyglutamylation showed a marked reduction in MTX uptake due to a decrease in Vmax without a significant change in Kt. These findings suggest the existence of membrane molecules like SQM1 protein that may indirectly affect MTX transport.
 ...
PMID:Congruence of SQM1 protein expression with methotrexate sensitivity and transport. 783 71