Type

Journal Article

Authors

M Clynes
F O'Sullivan
M Center
M A Izquierdo
R J Scheper
A Masterson
R N Amhlaoibh
A M Larkin
I Cleary
E Moran

Subjects

Microbiology

Topics
p glycoprotein vault ribonucleoprotein particles humans metabolism multidrug resistance associated proteins immunohistochemistry female chemistry drug resistance neoplasm antibiotics antineoplastic tumor markers biological neoplasm proteins blotting western ovarian neoplasms drug resistance multiple polymerase chain reaction tumor cells cultured atp binding cassette transporters major vault protein doxorubicin

Co-expression of MDR-associated markers, including P-170, MRP and LRP and cytoskeletal proteins, in three resistant variants of the human ovarian carcinoma cell line, OAW42. (1997)

Abstract Variants of the human ovarian carcinoma cell line, OAW42, exhibiting low-level intrinsic resistance (OAW42-SR) and drug-induced higher-level resistance (OAW42-A1 & OAW42-A), were studied along with a sensitive clonal population (OAW42-S) which was isolated from OAW42-SR. Expression of the MDR-associated protein P-170, the more recently discovered LRP (lung resistance-related protein) and MRP (multidrug resistance-associated protein), topoisomerase II alpha and beta, GST pi and the cytoskeletal proteins, cytokeratin 8 and vimentin, were studied (using immunocytochemistry and Western blotting techniques) in conjunction with drug (doxorubicin) accumulation and subcellular distribution. Expression of mRNA for P-170, MRP, topoisomerase 11 alpha and beta and GST pi was studied using RT-PCR (reverse transcriptase polymerase chain reaction). Results indicate differential co-expression of four MDR-associated parameters (P-170, MRP, LRP and reduced topoisomerase II alpha and beta) in the OAW42-SR and OAW42-A1 variants, whereas resistance in the OAW42-A variant appeared to be mainly P-170 mediated. Comparable amounts of MRP and greater amounts of LRP were detected in the OAW42-S cells compared to the OAW42-SR variant (which showed increased resistance compared to the OAW42-S cells), but all cell lines expressed similar low-level amounts of MRP mRNA (by RT-PCR). GST pi levels did not differ markedly between variants. Increased levels of the cytoskeletal proteins were observed with increasing levels of resistance. The relative resistance of the variants, OAW42-SR and OAW42-A1, compared with OAW42-S was seen to change during increased serial passaging of the cells. There was greater drug accumulation by the sensitive OAW42-S cell line compared with that of the resistant variants, particularly the most highly resistant OAW42-A cells. Both verapamil and cyclosporin A effectively restored the accumulation defects seen in the resistant variants, cyclosporin A being the more effective of the two. Sub-cellular location of drug was predominantly in the nucleus with maximum levels seen in the sensitive OAW42-S variant and minimum levels in the most resistant OAW42-A clone.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

M Clynes, F O'Sullivan, M Center, M A Izquierdo, R J Scheper, A Masterson, R N Amhlaoibh, A M Larkin, I Cleary, E Moran

Experts in our system

1
Martin Clynes
Dublin City University
Total Publications: 209
 
2
Finbarr O'Sullivan
Dublin City University
Total Publications: 21
 
3
Annemarie Larkin
Dublin City University
Total Publications: 25