Type

Journal Article

Authors

M Clynes
K J Scanlon
G Nuñez
C Daly
C O'Loughlin
S Touhey
I Cleary
M Heenan
R Nicamhlaoibh

Subjects

Microbiology

Topics
carcinoma squamous cell tumor cells cultured genetics apoptosis pathology metabolism rna messenger doxorubicin in situ nick end labeling biosynthesis antineoplastic agents lung neoplasms genes bcl 2 therapeutic use genetic variation gene expression regulation neoplastic drug resistance neoplasm humans p glycoprotein physiology drug resistance multiple

Altered expression of mRNAs for apoptosis-modulating proteins in a low level multidrug resistant variant of a human lung carcinoma cell line that also expresses mdr1 mRNA. (1999)

Abstract An in vitro model that might be relevant to cancer cell chemoresistance in vivo was generated by exposing the human lung carcinoma clonal cell line DLKP-SQ to 10 sequential pulses of pharmacologically attainable doses of doxorubicin. The resistant variant, DLKP-SQ/10p, was found to be cross-resistant to doxorubicin (10x), vincristine (43x), etoposide (3x), sodium arsenate (3x), paclitaxel (38x) [which could imply overexpression of P-glycoprotein (P-gp) and possibly increased multidrug resistance-associated protein activity] and 5-fluorouracil (4x), but slightly sensitized to carboplatin. Analysis of mRNA levels in the resistant variant revealed overexpression of mdr1 mRNA without significant alteration in mrp, Topo. IIalpha, GSTpi, dhfr or thymidylate synthase mRNA levels. Overexpression of the anti-apoptotic bcl-xL transcript and the pro-apoptotic bax mRNA was also detected but no alterations in bcl-2 or bag-1 mRNA levels were observed. Resistance to a P-gp-associated drug, doxorubicin, could be reversed with P-gp circumventing agents such as cyclosporin A and verapamil, but these substances had no effect on resistance to 5-fluorouracil. Overexpression of the pro-apoptotic bcl-xS gene in the DLKP-SQ/10p line partially reversed resistance not only to P-gp-associated drugs but also to 5-fluorouracil, indicating that the ratio of bcl family members may be important in determining sensitivity to chemotherapeutic drug-induced apoptosis.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

M Clynes, K J Scanlon, G Nuñez, C Daly, C O'Loughlin, S Touhey, I Cleary, M Heenan, R Nicamhlaoibh

Experts in our system

1
Martin Clynes
Dublin City University
Total Publications: 209
 
2
C Daly
Trinity College Dublin
Total Publications: 15