GROWTH-REGULATION BY ALL-TRANS-RETINOIC ACID AND RETINOIC ACID RECEPTOR MESSENGER RIBONUCLEIC-ACIDS EXPRESSION IN GASTRIC-CANCER CELLS

Retinoic acid has been recognised as a pivotal compound in cell differ entiation, proliferation and malignant transformation. We investigated the effects of all-trans-retinoic acid on cell growth and the express ion of retinoid nuclear receptor mRNAs in gastric cancer cells in vitr o. Cell growth was quantified by measuring total cellular DNA. The gro wth of two of the five gastric cancer cell lines tested (SC-M1 and TSG H9201) was inhibited by all-trans-retinoic acid at concentrations rang ing from 1 x 10(-8) M to 1 x 10(-6) M. Growth inhibition was associate d with G0/G1 phase arrest as determined by flow cytometric analysis. N orthern blot analysis showed that all five cell lines expressed mRNA f or retinoic acid receptors alpha and retinoic x receptor alpha and bet a. Retinoic acid receptor beta mRNA was only expressed in TSGH9201 and TMK-1 gastric cancer cell lines. Two RAR gamma mRNA transcripts (3.2 and 3.0 kb) were detected in SC-M1 and TSGH9201 cells. RA-resistant ce lls had markedly decreased levels of the 3.2 kb RAR gamma transcript. All-trans-retinoic acid had a cytostatic effect on the growth of some gastric cancer cells, which may be associated with the expression of r etinoic acid receptors.