Gastric Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 21, 2006; 12(19): 3000-3005
Published online May 21, 2006. doi: 10.3748/wjg.v12.i19.3000
Selective inhibition of cell growth by activin in SNU-16 cells
Young Il Kim, Hee Joo Lee, Inkoo Khang, Byung-Nam Cho, Ha Kyu Lee
Young Il Kim, East-West Medical Research Institute, Kyung Hee University, Seoul, South Korea
Hee Joo Lee, Department of Laboratory Medicine, Kyung Hee University, College of Medicine, Seoul, South Korea
Inkoo Khang, School of Biological Sciences, Seoul National University, Seoul, South Korea
Byung-Nam Cho, Ha Kyu Lee, Department of Life Sciences, The Catholic University of Korea, Puchon, South Korea
Author contributions: All authors contributed equally to the work
Supported by the Research Fund 2003 from the Catholic University of Korea
Correspondence to: Dr. Ha Kyu Lee, Department of Life Sciences, The Catholic University of Korea, 43-1 Yokkok 2-dong, Wonmi-gu, Puchon 420-743, Korea. lhk52012@catholic.ac.kr
Telephone: +82-2-21644356 Fax: +82-2-21644765
Received: April 14, 2005
Revised: July 21, 2005
Accepted: July 28, 2005
Published online: May 21, 2006
Abstract

AIM: To investigate whether activin regulates the cell proliferation of human gastric cancer cell line SNU-16 through the mRNA changes in activin receptors, Smads and p21CIP1/WAF1.

METHODS: The human gastric cancer cell lines were cultured, RNAs were purified, and RT-PCRs were carried out with specifically designed primer for each gene. Among them, the two cell lines SNU-5 and SNU-16 were cultured with activin A for 24, 48 and 72 h. The cell proliferation was measured by MTT assay. For SNU-16, changes in ActRIA, ActRIB, ActRIIA, ActRIIB, Smad2, Smad4, Smad7, and p21CIP1/WAF1 mRNAs were detected with RT-PCR after the cells were cultured with activin A for 24, 48 and 72 h.

RESULTS: The proliferation of SNU-16 cells was down regulated by activin A whereas other cells showed no change. Basal level of inhibin/activin subunits, activin receptors, Smads, and p21CIP1/WAF1 except for activin βB mRNAs was observed to have differential expression patterns in the human gastric cancer cell lines, AGS, KATO III, SNU-1, SNU-5, SNU-16, SNU-484, SNU-601, SNU-638, SNU-668, and SNU-719. Interestingly, significantly higher expressions of ActR IIA and IIB mRNAs were observed in SNU-16 cells when compared to other cells. After activin treatment, ActR IA, IB, and IIA mRNA levels were decreased whereas ActR IIB mRNA level increased in SNU-16 cells. Smad4 mRNA increased for up to 48 h whereas Smad7 mRNA increased sharply at 24 h and returned to the initial level at 48 h in SNU-16 cells. In addition, expression of the p21CIP1/WAF1, the mitotic inhibitor, peaked at 72 h after activin treatment in SNU-16 cells.

CONCLUSION: Our results suggest that inhibition of cell growth by activin is regulated by the negative feedback effect of Smad7 on the activin signaling pathway, and is mediated through p21CIP1/WAF1 activation in SNU-16 cells.

Keywords: Human gastric cancer cell lines; Activin A; Cell proliferation; Activin receptors; Smads; p21CIP1/WAF1