Retinoic acid down-regulates VPAC(1) receptors and TGF-beta 3 but up-regulates TGF-beta 2 in lung cancer cells.
The effects of retinoic acid (RA) on lung cancer cells were investigated. Both all-trans (t-RA) and 13-cis RA (c-RA) decreased specific (125)I-VIP binding to NCI-H1299 cells in a time- and concentration-dependent manner. After 20 hr, 30 microM t-RA decreased specific (125)I-VIP binding by 60%. By Scatchard analysis, the density of VIP binding sites but not the affinity was reduced by 42%. NCI-H1299 VPAC(1) receptor mRNA was reduced by 48%. VIP caused a 3-fold elevation in the NCI-H1299 cAMP, and the increase in cAMP caused by VIP was reduced by 38% if the NCI-H1299 cells were treated with t-RA. Using the MTT assay, 3 microM t-RA and 3 microM c-RA inhibited NCI-H1299 proliferation by 60 and 23% respectively. Also, transforming growth factor (TGF)-beta2 increased after treatment of NCI-H1299 cells with t-RA whereas TGF-beta 1 mRNA was unaffected and TGF-beta 3 mRNA was decreased. These results suggest that RA may inhibit lung cancer growth by down-regulating VPAC(1) receptor and TGF-beta 3 mRNA but up-regulating TGF-beta 2 mRNA.
Jakowlew
S B
SB
Cell & Cancer Biology Dept., Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA.
Zakowicz
H
H
Moody
T W
TW
D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D014212:Tretinoin; D000242:Cyclic AMP