Growth regulation by all-trans-retinoic acid and retinoic acid receptor messenger ribonucleic acids expression in gastric cancer cells

Tyrosine-kinase expression profiles in human gastric cancer cell lines and their modulations with retinoic acids

“…RAR and RXR can also be phosphorylated by protein kinases (Tahayato et al, 1993). In a previous report on RARs' and RXRs' Northern mRNA expression level of gastric cancer cell lines (Shyu et al, 1995), enhanced expression of RARa/RARg was observed in SC-M1 cells and enhanced RARb level was found in TSGH cells. Both RA-sensitive cell lines (SC-M1 and TSGH) had also increased RXRa expression, but only TSGH had higher RXRb expression transcript.…”

“…We first selected RA for our studies, since it directly modulates gene expressions following its binding to RAR or RXR receptors. In addition, RA was shown to suppress gastric cancer cell growth in vitro (Shyu et al, 1995;Naka et al, 1997). We used both 9-cis-RA and all-trans-RA and three RA responsive cell lines (NUGC, SC-M1, TSGH) in this study.…”

“…Retinoic acid was dissolved in dimethyl sulphfoxide (DMSO) under subdued light in a tissue culture hood. Three cell lines were selected for RA treatment based on an earlier report of their sensitivity to RA (Shyu et al, 1995) as well as their tolerance to serum-free culture conditions. Since serum could contain retinoids and other steroid hormones, serum-free culture conditions were preferable to reduce the background.…”

“…However, the present study is the first to show the modulation of eph and hek5 by RA treatment in human gastric cancer cell lines. In a reported RA-resistant cell line (AGS) (Shyu et al, 1995), basal levels of hek5 and c-erbB2/neu expression were markedly elevated in comparison with those of RA-sensitive cell lines (Figure 6). Since amplification of c-erbB2/neu could lead to drug-resistant phenotypes in tumour cells (Yu et al, 1996), it would be interesting to investigate if hek5 kinase is also involved in such mechanisms.…”

“…Deficiencies in the metabolism of retinoids are associated with severe defects of vertebrate embryonic development (Gudas, 1992;Chambon, 1994). This reagent has been used in the treatment of acute promyelocytic leukaemia with good success (Huang et al, 1988), and recently it was shown to suppress the growth of gastric cancer cell lines (Shyu et al, 1995;Naka et al, 1997). The RA signalling pathway involves specific high-affinity receptors, which belong to ligand -inducible transcription factors (Chambon, 1996).…”