Document Detail


CRABP I expression and the mediation of the sensitivity of human tumour cells to retinoic acid and irradiation.
MedLine Citation:
PMID:  14713576     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To examine the role cytoplasmic retinoic acid binding protein type 1 (CRABP I) and retinoic acid receptor beta 2 (RAR-beta 2) in mediating radiosensitization of human tumour cells in vitro by retinoic acid. MATERIALS AND METHODS: Human squamous cell carcinoma cell lines of different types were treated with retinoic acid followed by irradiation. Radiation response under drug treatment was detected by colony-formation assay. mRNA and protein expression levels of CRABP I, RAR-beta and cyclin D1 were investigated under different treatment conditions by room temperature polymerase chain reaction and Western blotting. The retinoic acid-sensitive cell line HTB35 was transfected for inducible CRABP I overexpression to test the role of this protein in modulating the sensitivity to retinoic acid and radiation as well as in regulating RAR-beta 2 and cyclin D1 expression. RESULTS: The basal CRABP I level clearly correlated with the clonogenic survival of tumour cells and normal fibroblasts after treatment with retinoic acid and ionizing irradiation (IR). Cells expressing high basal CRABP I were more resistant to combined retinoic acid radiation treatment than cells with low basal expression. Overexpression of CRABP I in retinoic acid-sensitive HTB35 cells induced a retinoic acid-insensitive phenotype resistant to combined treatment with retinoic acid and radiation. This effect was independent of RAR-beta 2 expression. CRABP I overexpression resulted in stimulated cyclin D1 expression indicating the dependency of this cell cycle control protein on retinoic acid metabolism. CONCLUSION: CRABP I plays an important role not only in mediating the retinoid effects, but also in modulating the radiation sensitivity of tumour cells after combined retinoic acid radiation treatment.
Authors:
M A Blaese; L Santo-Hoeltje; H P Rodemann
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation biology     Volume:  79     ISSN:  0955-3002     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2004-01-09     Completed Date:  2004-04-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  981-91     Citation Subset:  IM; S    
Affiliation:
Section of Radiobiology and Molecular Environmental Research, Eberhard-Karls-University Tuebingen, Roentgenweg 11, D-72076 Tuebingen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor / metabolism,  pathology,  radiation effects
Cell Survival / drug effects,  radiation effects
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Fibroblasts / cytology,  drug effects*,  metabolism,  radiation effects*
Humans
Neoplasms / metabolism*,  pathology*
Radiation Tolerance / drug effects*
Radiation-Sensitizing Agents / pharmacology
Receptors, Retinoic Acid / metabolism*
Tretinoin / pharmacology*
Tumor Stem Cell Assay
Chemical
Reg. No./Substance:
0/Radiation-Sensitizing Agents; 0/Receptors, Retinoic Acid; 0/retinoic acid binding protein I, cellular; 0/retinoic acid receptor beta; 302-79-4/Tretinoin

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