Cellular retinoic acid binding protein I: expression and functional influence in renal cell carcinoma.
Despite the known anti-proliferative and tumor-suppressive effects seen with retinoic acid (RA), treatment of metastatic renal cell carcinoma (RCC) failed to meet the initial expectations. As the exact mechanisms of action of RA and especially the role of the cellular RA binding proteins (CRABP) have not been elucidated yet, we investigated the expression of CRABP-I and its potential influence on RA response in RCC. Real-time RT-PCR analysis disclosed a significant lack of CRABP-I expression in four RCC cell lines and 12 primary RCC samples; in contrast, high expression levels were found in the respective adjacent normal kidney tissue. To further investigate the impact of CRABP-I on RA response in RCC, A-498 RCC cells were employed as a cellular model system. CRABP-I was stably transfected into A-498 cells which consequently displayed substantial resistance to all-trans (ATRA) and 9-cis RA compared to vector controls lacking CRABP-I. Comparison of gene expression profiles of ATRA-treated CRABP-I-expressing A-498 cells and vector controls revealed specific regulation of 54 of approximately 20,000 genes tested on a selected human CodeLink UniSet Bioarray, with a prominent modulation of genes involved in transcriptional control, signaling, apoptosis, cell cycle regulation and metabolism. The genetic changes reported here contribute to a better understanding of the role of RA in RCC. They also provide new insights into CRABP-I-mediated signaling and gene expression.
Pfoertner
Susanne
S
Department of Cell Biology and Immunology, German Research Center for Biotechnology, Braunschweig, Germany.
Goelden
Ulrike
U
Hansen
Wiebke
W
Toepfer
Tanja
T
Geffers
Robert
R
Ukena
Sya N
SN
von Knobloch
Rolf
R
Hofmann
Rainer
R
Buer
Jan
J
Schrader
Andres J
AJ
D000368:Aged; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082927:retinoic acid binding protein I, cellular; D014212:Tretinoin