PMID- 16150928
OWN - NLM
STAT- MEDLINE
DCOM- 20060119
LR  - 20131121
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 68
IP  - 6
DP  - 2005 Dec
TI  - A novel group of genes regulates susceptibility to antineoplastic drugs in highly 
      tumorigenic breast cancer cells.
PG  - 1747-56
AB  - Doxorubicin is an anthracycline antibiotic used for cancer chemotherapy. The 
      utility of doxorubicin is limited by its inability to kill all of the cells 
      within a tumor and by resistant cells emerging from the treated population. We 
      have screened for genes that regulate doxorubicin susceptibility in highly 
      tumorigenic breast cancer cells by cDNA microarray and RNA interference (RNAi) 
      analysis, and we have identified genes associated with both proliferation and 
      cell cycle arrest after doxorubicin treatment. We confirmed that MDA-MB-231 cells 
      treated with doxorubicin induce the expression of carbonic anhydrase II (CAII), 
      inhibitor of differentiation/DNA binding 2 (Id2), activating transcription factor 
      3 (Atf3), and the phosphatidylinositol 3-kinase 55-kDa regulatory subunit p55PIK. 
      These genes were induced at different times and with varying specificities to 
      different chemotherapeutic drugs. In addition to being induced at the 
      transcriptional level, the CAII and clusterin proteins were elevated after 
      doxorubicin treatment. CAII, Id2, p55PIK, and clusterin were not altered by 
      doxorubicin in MCF-7 cells, a weakly tumorigenic cell line used in previous 
      studies of doxorubicin-regulated gene expression. By inhibiting gene expression 
      using RNAi, we found that CAII and clusterin increase cell survival after 
      doxorubicin treatment, whereas Id2 increases susceptibility to doxorubicin. Our 
      results support a model in which highly tumorigenic breast cancer cells induce a 
      transcriptional response to doxorubicin that is distinct from less malignant 
      cells. The induced genes regulate drug susceptibility positively and negatively 
      and may be novel targets for therapeutic intervention.
FAU - Mallory, Julia C
AU  - Mallory JC
AD  - Department of Molecular and Biomedical Pharmacology, Markey Cancer Center, MS-305 
      University of Kentucky Medical Center, University of Kentucky, Lexington, 
      Kentucky 40536, USA.
FAU - Crudden, Gerard
AU  - Crudden G
FAU - Oliva, Amelia
AU  - Oliva A
FAU - Saunders, Christopher
AU  - Saunders C
FAU - Stromberg, Arnold
AU  - Stromberg A
FAU - Craven, Rolf J
AU  - Craven RJ
LA  - eng
GR  - P20-RR16481/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20050908
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Antineoplastic Agents)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Breast Neoplasms/drug therapy/genetics/*pathology
MH  - Cell Cycle/genetics
MH  - Cell Growth Processes/genetics
MH  - Cell Line, Tumor
MH  - Doxorubicin/*pharmacology
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Transcription, Genetic/drug effects
EDAT- 2005/09/10 09:00
MHDA- 2006/01/20 09:00
CRDT- 2005/09/10 09:00
PHST- 2005/09/10 09:00 [pubmed]
PHST- 2006/01/20 09:00 [medline]
PHST- 2005/09/10 09:00 [entrez]
AID - mol.105.016519 [pii]
AID - 10.1124/mol.105.016519 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2005 Dec;68(6):1747-56. doi: 10.1124/mol.105.016519. Epub 2005 Sep 
      8.