The effect pathway of retinoic acid through regulation of retinoic acid receptor alpha in gastric cancer cells.

Abstract:

AIM:To evaluate the role of RARalpha gene in mediating the growth inhibitory effect of all-trans retinoic acid (ATRA) on gastric cancer cells. METHODS:The expression levels of retinoic acid receptors (RARs) in gastric cancer cells were detected by Northern blot. Transient transfection and chlorophenicol acetyl transferase (CAT) assay were used to show the transcriptional activity of beta retinoic acid response element (betaRARE) and AP-1 activity. Cell growth inhibition was determined by MTT assay and anchorage-independent growth assay, respectively. Stable transfection was performed by the method of Lipofectamine, and the cells were screened by G418. RESULTS:ATRA could induce expression level of RARalpha in MGC80-3, BGC-823 and SGC-7901 cells obviously, resulting in growth inhibition of these cell lines. After sense RARalpha gene was transfected into MKN-45 cells that expressed rather low level of RARalpha and could not be induced by ATRA, the cell growth was inhibited by ATRA markedly. In contrast, when antisense RARalpha gene was transfected into BGC-823 cells, a little inhibitory effect by ATRA was seen, compared with the parallel BGC-823 cells. In transient transfection assay, ATRA effectively induced transcriptional activity of betaRARE in MGC80-3, BGC-823, SGC-7902 and MKN/RARalpha cell lines, but not in MKN-45 and BGC/aRARalpha cell lines. Similar results were observed in measuring-antiAP-1 activity by ATRA in these cancer cell lines. CONCLUSION:ATRA inhibits the growth of gastric cancer cells by up-regulating the level of RARalpha RARalpha is the major mediator of ATRA action in gastric cancer cells; and adequate level of RARalpha is required for ATRA effect on gastric cancer cells.

journal_name

World J Gastroenterol

authors

Liu S,Wu Q,Chen ZM,Su WJ

doi

10.3748/wjg.v7.i5.662

keywords:

subject

Has Abstract

pub_date

2001-10-01 00:00:00

pages

662-6

issue

5

eissn

1007-9327

issn

2219-2840

journal_volume

7

pub_type

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