PMID- 17475205
OWN - NLM
STAT- MEDLINE
DCOM- 20071001
LR  - 20190412
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 464
IP  - 1
DP  - 2007 Aug 1
TI  - Mechanisms of resistance and adaptation to thapsigargin in androgen-independent 
      prostate cancer PC3 and DU145 cells.
PG  - 19-27
AB  - Cells with increasing resistance to the sarcoplasmic/endoplasmic reticulum 
      Ca(2+)-ATPase (SERCA) inhibitor thapsigargin (TG), ranging from 60-fold 
      (PC3/TG(10) cells) to 1350-fold (PC3/TG(2000) cells), were derived from PC3 
      cells. SERCA2 is overexpressed in all PC3/TG cells but retains sensitivity to TG. 
      siRNA-mediated downregulation of SERCA completely or partially reverses TG 
      resistance in PC3/TG(10) or PC3/TG(2000) cells, respectively; thus SERCA 
      overexpression mediates resistance in PC3/TG(10) cells but is not the only 
      resistance mechanism in PC3/TG(2000) cells. By contrast, SERCA is not 
      overexpressed in TG-resistant DU145/TG cells derived from DU145 cells. DU145/TG 
      cells retain resistance while in PC3/TG cells resistance decreases upon removal 
      of TG selection. The transport proteins PGP/BCRP/MRP1 and anti-apoptotic proteins 
      Bcl2/Bcl(XL) are not involved in mediating resistance in either cell line. PARP 
      and caspase 3 cleavage in response to other drugs demonstrate that the apoptotic 
      pathways tested remain intact in these cells. Further, no cross-resistance occurs 
      to other drugs. Thus, novel TG-specific resistance mechanisms are recruited by 
      these cancer cells.
FAU - Lee, Dong I
AU  - Lee DI
AD  - Department of Biochemistry and Molecular Biology, University of Maryland School 
      of Medicine, Baltimore, MD 21201, USA.
FAU - Sumbilla, Carlota
AU  - Sumbilla C
FAU - Lee, Myounghee
AU  - Lee M
FAU - Natesavelalar, Chidambaram
AU  - Natesavelalar C
FAU - Klein, Michael G
AU  - Klein MG
FAU - Ross, Douglas D
AU  - Ross DD
FAU - Inesi, Giuseppe
AU  - Inesi G
FAU - Hussain, Arif
AU  - Hussain A
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070416
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Androgens)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (RNA, Small Interfering)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - EC 7.2.2.10 (ATP2A2 protein, human)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Androgens/*metabolism
MH  - Apoptosis
MH  - Calcium/metabolism
MH  - Cell Line, Tumor
MH  - Cytosol/metabolism
MH  - Drug Resistance
MH  - *Drug Resistance, Neoplasm
MH  - Enzyme Inhibitors/*pharmacology
MH  - Gene Silencing
MH  - Humans
MH  - Male
MH  - Prostatic Neoplasms/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
MH  - Thapsigargin/*chemistry/*pharmacology
EDAT- 2007/05/04 09:00
MHDA- 2007/10/02 09:00
CRDT- 2007/05/04 09:00
PHST- 2007/01/08 00:00 [received]
PHST- 2007/03/29 00:00 [revised]
PHST- 2007/03/30 00:00 [accepted]
PHST- 2007/05/04 09:00 [pubmed]
PHST- 2007/10/02 09:00 [medline]
PHST- 2007/05/04 09:00 [entrez]
AID - S0003-9861(07)00178-6 [pii]
AID - 10.1016/j.abb.2007.03.040 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2007 Aug 1;464(1):19-27. doi: 10.1016/j.abb.2007.03.040. 
      Epub 2007 Apr 16.