β-Catenin expression is associated with cell invasiveness in pancreatic cancer

Abstract

Background/aims: This study was tried to determine the role of β-catenin in invasion in pancreatic cancer.

Methods: We analyzed cancer invasiveness according to β-catenin expression in pancreatic cancer cell line. We also investigated the change in cancer invasiveness when β-catenin expression was changed. To enhance β-catenin activity, we treated low β-catenin cancer cell line, PANC1, with Wnt-3a conditioned media and transected β-catenin. We also treated high β-catenin expressing cell line, BxPC3, with XAV939, β-catenin inhibitor and siRNA for β-catenin to inhibit β-catenin expression.

Results: The high β-catenin expressing cancer cell line, BxPC3 showed higher invasiveness, and low β-catenin expressing cell lines, PANC1and MIA-PaCa-2, were less invasive. By adding the Wnt-3a conditioned media or performing transfection with β-catenin in PANC1, cell invasiveness was increased (p < 0.05 and p < 0.01, respectively). On inhibition of β-catenin by XAV939 and siRNA in BxPC3 cell line, invasiveness was significantly decreased (p < 0.01). It was not correlated with the expression of cluster of differentiation 44 (CD44) or CD44 variant 6 (CD44v6), the invasion related protein. On analysis of association with metastasis in human tissue, Wnt-3a expression was statistically correlated with the development of metastasis (p = 0.029).

Conclusion: Based on our data, β-catenin may be involved in cancer invasion in pancreatic cancer, and it is not associated with CD44, the invasion related protein.

Keywords: Beta-catenin; Invasiveness; Pancreatic neoplasms.

Figure 1.

Expression of β-catenin. (A) Expression of β-catenin in each pancreatic cancer cell lines. (B) After Wnt-3a conditioned media, β-catenin expression was significantly increased and maximum at 6 hours. GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Figure 2.

(A, B) Transwell invasion assay. The pancreatic cell was most invasiveness in BxPC3 cell line, not associated with cluster of differentiation 44 (CD44) or CD44 variant 6 (CD44v6) expression.

Figure 3.

Change of cell invasion after β-catenin activation. (A) The cell invasion was increased without change of cluster of differentiation 44 (CD44) or CD44 variant 6 (CD44v6) expression after Wnt-3a media treatment. (B) The cell invasion was also increased after transfection β-catenin both wild and mutant S33Y type without dependent CD44 or CD44V6 expression. GAPDH, glyceraldehyde 3-phosphate dehydrogenase. ^a p < 0.05, ^b p < 0.01.

Figure 4.

Change of cell invasion after β-catenin inhibition. (A) The cell invasion was decreased after β-catenin expression inhibition by XAV939 (Wnt/β-catenin signaling inhibitor). (B) The cell invasion was also decreased after treatment of siRNA for β-catenin. GAPDH, glyceraldehyde 3-phosphate dehydrogenase. ^a p < 0.01.

Figure 5.

Survival outcome according to Wnt expression. (A) Overall survival for β-catenin (15.3 months vs. 9.1 months, p = 0.703). (B) Overall survival for Wnt-3a (12.3 months vs. 8.2 months, p = 0.363). (C) Overall survival for Wnt-5a (12.4 months vs.9.1 months, p = 0.401).