Growth inhibition of cultured human gastric cancer coils by 9-cis-retinoic acid with induction of cdk inhibitor Waf1/Cip1/Sdi1/p21 protein

被引:29
作者
Naka, K
Yokozaki, H
Domen, T
Hayashi, K
Kuniyasu, H
Yasui, W
Lotan, R
Tahara, E
机构
[1] HIROSHIMA UNIV,SCH MED,DEPT PATHOL 1,MINAMI KU,HIROSHIMA 734,JAPAN
[2] UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030
关键词
D O I
10.1046/j.1432-0436.1997.6150313.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The effect of 9-cis-retinoic acid (9-cis-RA) on the growth of eight gastric cancer cell lines was related to their transcription levels of mRNAs for retinoid receptors. Northern blot analysis showed that seven (TMK-1, MKN-1, -28, -45, -74, HSC-39, KATO-III) out of eight gastric cancer cell lines synthesized mRNAs for retinoic acid receptors (RARs) and retinoid X receptor-alpha (RXR-alpha). MKN-7 cells did not transcribe either RARs or RXR-alpha at the mRNA level although they appeared to have no alterations at the gene level. The growth of all of the cell Lines except for MKN-7 cells was inhibited by 1 x 10(-6) M 9-cis-RA. Cell cycle distribution analysis revealed that G(0)-G(1) arrest was not induced by exposure to 9-cis-RA in the sensitive TMK-1 and KATO-III cells or the resistant MKN-7 cells. Interestingly, 9-cis-RA temporarily increased the amount of the cyclin dependent kinase (cdk) inhibitor, Waf1/Cip1/Sdi1/p21 protein, and also reduced the amount of cdk-7, epidermal growth factor receptor (EGFR) and cyclin D1 proteins, followed by reduction in phosphorylation of the product of the retinoblastoma tumor suppressor gene (Rb) in the sensitive TMK-1 cells, but not in the resistant MKN-7 cells. These results suggest that 9-cis-RA has a cytostatic effect on gastric cancer cells that synthesize the receptor molecules through cell cycle regulatory machinery.
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页码:313 / 320
页数:8
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