PMID- 15572038
OWN - NLM
STAT- MEDLINE
DCOM- 20050218
LR  - 20191210
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 303
IP  - 1
DP  - 2005 Feb 1
TI  - Cis-retinol dehydrogenase: 9-cis-retinol metabolism and its effect on 
      proliferation of human MCF7 breast cancer cells.
PG  - 183-96
AB  - 9-Cis-retinoic acid (RA) suppresses cancer cell proliferation via binding and 
      activation of nuclear receptors, retinoid X receptors (RXRs). In vivo, 9-cis-RA 
      is formed through oxidation of 9-cis-retinol by cis-retinol dehydrogenase (cRDH), 
      an enzyme that we characterized previously. Since 9-cis-RA is a potent inhibitor 
      of breast cancer cell proliferation, we hypothesized that overexpression of cRDH 
      in breast cancer cells would result in increased production of 9-cis-RA, which in 
      turn would suppress cell proliferation. To investigate this hypothesis, MCF7 
      human breast carcinoma cells were transduced with cRDH cDNA (LRDHSN/MCF7), and 
      the growth kinetics and retinoid profiles of cells were examined following 
      treatment with 9-cis-retinol. LRDHSN/MCF7 cells showed a marked reduction in cell 
      numbers (60-80%) upon treatment with 9-cis-retinol compared to vehicle alone. 
      Within 24 h of treatment, approximately 75% of the 9-cis-retinol was taken up and 
      metabolized by LRDHSN/MCF7 cells. Despite the rapid uptake and oxidation of 
      9-cis-retinol to 9-cis-retinal, 9-cis-RA was not formed in these cells. We detect 
      at least one novel metabolite formed from both 9-cis-retinol and 9-cis-retinal 
      that may play a role in inhibition of MCF7 cell proliferation. Our studies 
      demonstrate that 9-cis-retinol in combination with cRDH inhibits breast cancer 
      cell proliferation by production of retinol metabolites other than RA.
FAU - Paik, Jisun
AU  - Paik J
AD  - Department of Pathobiology, University of Washington, Seattle, WA 98195, United 
      States.
FAU - Blaner, William S
AU  - Blaner WS
FAU - Swisshelm, Karen
AU  - Swisshelm K
LA  - eng
GR  - DK35816/DK/NIDDK NIH HHS/United States
GR  - DK52444/DK/NIDDK 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  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Diterpenes)
RN  - 0 (Retinoid X Receptors)
RN  - 514-85-2 (9-cis-retinal)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.105 (retinol dehydrogenase 5)
RN  - RR725D715M (Retinaldehyde)
SB  - IM
MH  - Alcohol Oxidoreductases/genetics/*metabolism
MH  - Breast Neoplasms/drug therapy/*enzymology
MH  - Cell Proliferation/*drug effects
MH  - Diterpenes
MH  - Female
MH  - Humans
MH  - Retinaldehyde/chemistry/*pharmacology
MH  - Retinoid X Receptors/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2004/12/02 09:00
MHDA- 2005/02/19 09:00
CRDT- 2004/12/02 09:00
PHST- 2004/06/05 00:00 [received]
PHST- 2004/09/22 00:00 [revised]
PHST- 2004/12/02 09:00 [pubmed]
PHST- 2005/02/19 09:00 [medline]
PHST- 2004/12/02 09:00 [entrez]
AID - S0014-4827(04)00569-5 [pii]
AID - 10.1016/j.yexcr.2004.09.019 [doi]
PST - ppublish
SO  - Exp Cell Res. 2005 Feb 1;303(1):183-96. doi: 10.1016/j.yexcr.2004.09.019.