PMID- 7907587
OWN - NLM
STAT- MEDLINE
DCOM- 19940418
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 11
DP  - 1994 Mar 18
TI  - Alterations in Ca2+ transport ATPase and P-glycoprotein expression can mediate 
      resistance to thapsigargin.
PG  - 7976-81
AB  - Resistance to the intracellular Ca2+ pump inhibitor thapsigargin (TG) is 
      associated with overexpression of both Ca2+ transport ATPase and the multidrug 
      resistance (mdr) transporter P-glycoprotein (pgp). This is supported by increased 
      resistance to TG following transfection of a functional pgp1 cDNA, and reversal 
      of TG resistance with known inhibitors of pgp function. However, pgp is unlikely 
      to represent the only mechanism of resistance to TG. Cell lines selected for high 
      levels of resistance to TG (250-fold) show only a 3.7-fold increase in pgp 
      expression and a 2-fold increase in cross-resistance to other drugs of the mdr 
      class. Overexpression of endogenous Ca2+ transport ATPase may represent a second 
      mechanism of resistance to TG. Increased Ca2+ ATPase expression (3-fold) is seen 
      in cells made resistant to TG, and TG resistance increases with the transfection 
      of a specific Ca2+ ATPase cDNA into DC-3F cells. If these transfectants are then 
      made resistant to TG, both the endogenous Ca2+ ATPase and the exogenously 
      transfected Ca2+ ATPase become overexpressed. These studies suggest that while TG 
      may be a substrate for pgp, acquired resistance to TG can involve alterations in 
      both pgp and Ca2+ ATPase expression. Additional, as yet unidentified, mechanisms 
      of resistance may be involved in resistance to TG.
FAU - Gutheil, J C
AU  - Gutheil JC
AD  - University of Maryland Cancer Center, Baltimore, Maryland 21201.
FAU - Hart, S R
AU  - Hart SR
FAU - Belani, C P
AU  - Belani CP
FAU - Melera, P W
AU  - Melera PW
FAU - Hussain, A
AU  - Hussain A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Azides)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (Dihydropyridines)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Terpenes)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - 5J49Q6B70F (Vincristine)
RN  - 63XR70204A (azidopine)
RN  - 67526-95-8 (Thapsigargin)
RN  - 78E4J5IB5J (Mitotane)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SML2Y3J35T (Colchicine)
RN  - ZS7284E0ZP (Daunorubicin)
SB  - IM
GS  - pgp
GS  - pgp1
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1
MH  - Animals
MH  - Azides/metabolism
MH  - Calcium-Transporting ATPases/antagonists & inhibitors/*biosynthesis
MH  - Carrier Proteins/*biosynthesis/metabolism
MH  - Cell Division
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Colchicine/toxicity
MH  - Cricetinae
MH  - Cricetulus
MH  - DNA, Complementary/metabolism
MH  - Dactinomycin/toxicity
MH  - Daunorubicin/toxicity
MH  - Dihydropyridines/metabolism
MH  - *Drug Resistance
MH  - *Gene Expression
MH  - Lung
MH  - Membrane Glycoproteins/*biosynthesis/metabolism
MH  - Mitotane/*pharmacology
MH  - Multigene Family
MH  - Substrate Specificity
MH  - Terpenes/metabolism/*toxicity
MH  - Thapsigargin
MH  - Transfection
MH  - Vincristine/toxicity
EDAT- 1994/03/18 00:00
MHDA- 1994/03/18 00:01
CRDT- 1994/03/18 00:00
PHST- 1994/03/18 00:00 [pubmed]
PHST- 1994/03/18 00:01 [medline]
PHST- 1994/03/18 00:00 [entrez]
AID - S0021-9258(17)37147-8 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Mar 18;269(11):7976-81.