Genetic basis for the increased expression of vacuolar H+ translocating ATPase genes upon imatinib treatment in human lymphoblastoid cells

Kulkarni, Hemant, Goring, Harald H. H., Curran, Joanne E., Diego, Vincent, Dyer, Thomas D., Cole, Shelley, Walder, Ken R., Collier, Greg R., Blangero, John and Carless, Melanie A. 2013, Genetic basis for the increased expression of vacuolar H+ translocating ATPase genes upon imatinib treatment in human lymphoblastoid cells, Cancer chemotherapy and pharmacology, vol. 71, no. 4, pp. 1095-1100.

Attached Files
Name Description MIMEType Size Downloads

Title Genetic basis for the increased expression of vacuolar H+ translocating ATPase genes upon imatinib treatment in human lymphoblastoid cells
Formatted title Genetic basis for the increased expression of vacuolar H+ translocating ATPase genes upon imatinib treatment in human lymphoblastoid cells
Author(s) Kulkarni, Hemant
Goring, Harald H. H.
Curran, Joanne E.
Diego, Vincent
Dyer, Thomas D.
Cole, Shelley
Walder, Ken R.
Collier, Greg R.
Blangero, John
Carless, Melanie A.
Journal name Cancer chemotherapy and pharmacology
Volume number 71
Issue number 4
Start page 1095
End page 1100
Total pages 6
Publisher Springer
Place of publication Heidelberg, Germany
Publication date 2013-04
ISSN 0344-5704
1432-0843
Keyword(s) chronic myeloid leukemia
metastasis
imatinib
microarray
Summary Purpose The role of v-ATPases in cancer biology is being increasingly recognized. Yeast studies indicate that the tyrosine kinase inhibitor imatinib may interact with the v-ATPase genes and alter the course of cancer progression. Data from humans in this regard are lacking.

Methods We constructed 55 lymphoblastoid cell lines from pedigreed, cancer-free human subjects and treated them with IC20 concentration of imatinib mesylate. Using these cell lines, we (i) estimated the heritability and differential expression of 19 genes encoding several subunits of the v-ATPase protein in response to imatinib treatment; (ii) estimated the genetic similarity among these genes; and (iii) conducted a high-density scan to find cis-regulating genetic variation associated with differential expression of these genes.

Results We found that the imatinib response of the genes encoding v-ATPase subunits is significantly heritable and can be clustered to identify novel drug targets in imatinib therapy. Further, five of these genes were significantly cis-regulated and together represented nearly half-log fold change in response to imatinib (p = 0.0107) that was homogenous (p = 0.2598).

Conclusions Our results proffer support to the growing view that personalized regimens using proton pump inhibitors or v-ATPase inhibitors may improve outcomes of imatinib therapy in various cancers.
Language eng
Field of Research 110201 Cardiology (incl Cardiovascular Diseases)
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30051494

Document type: Journal Article
Collection: School of Medicine
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in TR Web of Science
Google Scholar Search Google Scholar
Access Statistics: 28 Abstract Views, 2 File Downloads  -  Detailed Statistics
Created: Tue, 19 Mar 2013, 14:19:49 EST by Jane Moschetti

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.