PMID- 9742259
OWN - NLM
STAT- MEDLINE
DCOM- 19981117
LR  - 20191210
IS  - 0305-1048 (Print)
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Linking)
VI  - 26
IP  - 19
DP  - 1998 Oct 1
TI  - Gene amplification and transcriptional upregulation of the sarco/endoplasmic 
      reticulum Ca2+ transport ATPase in thapsigargin-resistant hamster smooth muscle 
      cells.
PG  - 4529-37
AB  - We have selected a series of cell lines from the parental Syrian hamster smooth 
      muscle cell line DDT1-MF2that are resistant to thapsigargin (TG), a specific 
      inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+transport ATPases 
      (SERCAs). Cells were selected for resistance to TG in the presence or absence of 
      cyclosporin (CSA), which is a competitive inhibitor of the multidrug transporter 
      p-glycoprotein (pgp). Since TG is a known substrate for pgp, selection for TG 
      resistance was carried out in the presence of CSA in an attempt to minimize the 
      contribution of pgp, and to identify the potential range of adaptive responses of 
      the SERCA pump itself, during the development of the TG-resistant phenotype. 
      Irrespective of whether the selection is carried out in the presence or absence 
      of CSA, pgp is overexpressed in the TG-resistant DDT1-MF2cells. SERCA protein is 
      also overproduced in the TG-resistant cell lines, which occurs through one of 
      several mechanisms. Included among these, is amplification of the SERCA gene and 
      enhanced transcription of the gene. Enhanced transcription is observed only upon 
      long-term selection and occurs through the SERCA gene proximal promoter elements. 
      Although SERCA transcription in wild-type cells is dependent upon the -284 to -72 
      bp region of the SERCA promoter, the TG-resistant cells utilize both the -284 to 
      -72 bp and the -72 to +80 bp promoter regions for enhanced SERCA transcription. 
      That is, additional elements within the -72 to +80 bp region are recruited in the 
      TG-resistant cells to allow for increased SERCA expression. A 
      post-transcriptional step may also be recruited by the TG-resistant cells in 
      their overall strategy to produce increased amounts of the SERCA protein. These 
      studies demonstrate that the DDT1-MF2cells can utilize different mechanisms which 
      lead to increased levels of SERCA protein as the cells adapt to inhibition of the 
      ATPase by TG.
FAU - Rishi, A K
AU  - Rishi AK
AD  - Division of Oncology, Department of Medicine, Greenebaum Cancer Center, 
      University of Maryland and Baltimore Veterans Affairs Medical Center, Baltimore, 
      MD, USA. Cincinnati, O.
FAU - Yu, M
AU  - Yu M
FAU - Tsai-Wu, J J
AU  - Tsai-Wu JJ
FAU - Belani, C P
AU  - Belani CP
FAU - Fontana, J A
AU  - Fontana JA
FAU - Baker, D L
AU  - Baker DL
FAU - Periasamy, M
AU  - Periasamy M
FAU - Hussain, A
AU  - Hussain A
LA  - eng
GR  - HL-52318-04/HL/NHLBI NIH HHS/United States
GR  - P01HL27867/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Enzyme Inhibitors)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
SB  - IM
MH  - Animals
MH  - Calcium-Transporting ATPases/antagonists & inhibitors/*genetics/metabolism
MH  - Cell Line
MH  - Cricetinae
MH  - Drug Resistance
MH  - Enzyme Inhibitors/*pharmacology
MH  - Gene Amplification
MH  - Muscle, Smooth/*drug effects/*enzymology
MH  - Promoter Regions, Genetic
MH  - Thapsigargin/*pharmacology
MH  - *Transcriptional Activation
MH  - Transfection
MH  - Up-Regulation
PMC - PMC147867
EDAT- 1998/09/22 00:00
MHDA- 1998/09/22 00:01
PMCR- 1998/10/01
CRDT- 1998/09/22 00:00
PHST- 1998/09/22 00:00 [pubmed]
PHST- 1998/09/22 00:01 [medline]
PHST- 1998/09/22 00:00 [entrez]
PHST- 1998/10/01 00:00 [pmc-release]
AID - gkb708 [pii]
AID - 10.1093/nar/26.19.4529 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 1998 Oct 1;26(19):4529-37. doi: 10.1093/nar/26.19.4529.