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. 2014 Sep 15;7(9):3037-44.
eCollection 2014.

Regenerating gene family member 4 promotes growth and migration of gastric cancer through protein kinase B pathway

Jiamiao Huang  1 , Ya Yang  1 , Jian Yang  1 , Xian Li  1
Affiliations

Regenerating gene family member 4 promotes growth and migration of gastric cancer through protein kinase B pathway

Jiamiao Huang et al. Int J Clin Exp Med. .

Abstract

Regenerating gene family member 4 (REG4), a secreted protein, is overexpressed in several cancers, including gastric cancer. The present study was undertaken to determine the roles of REG4 in the growth of gastric cancer in the nude mice and in the proliferation and migration in human gastric cancer cell line and its downstream signaling pathway. Gastric cancer models were elicited by intraperitoneally injecting MKN45 human gastric cancer cells and the tumor size was measured every other day. The expressions of REG4 mRNA and protein were increased in the gastric cancer tissues from gastric cancer patients. REG4 increased the gastric tumor weight and size in the nude mice, and promoted the proliferation and migration of gastric cancer cells MKN45. Adeno-associated viral (AAV)-mediated knockdown of REG4 decreased the gastric tumor weight and size in the nude mice, and suppressed the proliferation and migration of MKN45 cells. REG4 increased the expression of phosphorylated protein kinase B (Akt). Triciribine hydrate (TCN), the inhibitor of Akt, decreased the gastric tumor weight and size in the nude mice and abolished REG4-induced weight and size increase of the tumor. TCN also inhibited proliferation and migration and abolished REG4-induced proliferation and migration increase of human gastric cell line MKN45. These results indicate that REG4 promotes the growth, proliferation and migration of gastric cancer through Akt pathway.

Keywords: Regenerating gene family member 4; gastric cancer; migration; proliferation; protein kinase B.

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Figures

Figure 1
Figure 1
Expression of regenerating gene family member 4 (REG4) in the gastric cancer tissue from gastric cancer patients. A: Expression of REG4 mRNA in the gastric cancer tissue from gastric cancer patients; B: Expression of REG4 protein in the gastric cancer tissue from gastric cancer patients. Values are mean ± SE. *P<0.05 versus Control. n=6 for each group.
Figure 2
Figure 2
Effects of regenerating gene family member 4 (REG4) on the gastric cancer. A: Effects of PBS and REG4 on the tumor weight and size in the mice; B: Effects of PBS and REG4 on the proliferation and migration of MKN45 cells. The tumor weight was measured 21 days after treatment and the tumor size was measured every other day. Values are mean ± SE. *P<0.05 versus PBS. n=6 for each group.
Figure 3
Figure 3
Effects of adeno-associated viral (AAV)-mediated knockdown of regenerating gene family member 4 (REG4) in the gastric cancer. A: The efficiency of the REG4-shRNA; B: Effects of REG4 knockdown on the tumor weight and size in the mice; C: Effects of REG4 knockdown on the proliferation and migration of MKN45 cells. The tumor weight and size were measured 21 days after treatment. Values are mean ± SE. *P<0.05 versus Control. n=6 for each group.
Figure 4
Figure 4
Effects of protein kinase B (Akt) inhibitor triciribine hydrate (TCN) on the gastric cancer. A: Effects of Akt inhibitor TCN on the tumor weight and size in the mice; B: Effects of Akt inhibitor TCN on the proliferation and migration of MKN45 cells. Values are mean ± SE. *P<0.05 versus PBS; and †P<0.05 versus REG4. n=6 for each group.
Figure 5
Figure 5
Effects of regenerating gene family member 4 (REG4) on protein kinase B (Akt) phosphorylation. REG4 increased the phosphorylation of Akt in the MKN45 cells 2 h after treatment. Values are mean ± SE. *P<0.05 versus PBS.
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