PTEN expression and suppression of proliferation are associated with Cdx2 overexpression in gastric cancer cells

Abstract

Abstract. The prognosis of gastric cancer (GC) is associated with Cdx2 and nuclear PTEN coexpression. This study aimed to determine the expression patterns of Cdx2 and PTEN in various GC tissues and cell lines to identify their relationship in GC. Immunohistochemistry was undertaken to assess the expression patterns of Cdx2 and PTEN in paraffin-embedded specimens of 228 GC patients who had undergone radical D2 gastrostomy with long-term follow-up. Cell growth and tumorigenicity were analyzed in the BGC823 cells with exogenous Cdx2 and any changes in the associated signaling pathways were interpreted in exogenous cdx2 expression and cdx2 knockdown. Cdx2 was found in the nuclei of GC cells in 43.4% (99/228) of the paraffin-embedded biopsies. A higher expression of nuclear PTEN was observed in 36.4% (83/228). Coexpression of Cdx2 and nuclear PTEN was detected in GC tumors (59/228, 25.9%) which correlated with the prognosis of advanced GC patients (p<0.001). The expression levels of Cdx2 and PTEN were variable in the different GC cell lines. However, the trends were similar between PTEN and Cdx2 in GC tissues and cell lines. High expression of Cdx2 and PTEN significantly reduced tumorigenicity in BGC823 cells compared with the empty vector control. Exogenous expression of Cdx2 triggered the upregulation of PTEN expression and decreased PI3K and pAkt expression and vice versa. The coexpression levels of PTEN and Cdx2 in GC tumors correlated with prognosis in GC patients. Cdx2 may play a role in the upregulation of PTEN by triggering PI3K/Akt inactivation in GC cells.

Roles of PTEN (Phosphatase and Tensin Homolog) in Gastric Cancer Development and Progression

“…These studies indicated that reduction or absence of PTEN expression is a dynamic process during the course of gastric cancer progression, and that PTEN levels can be used as an indicator to diagnose the pathological state of gastric cancer. Other studies exploring the role and mechanism of action of PTEN in gastric cancer, found similar results Bai et al, 2013;Li et al, 2013).…”

PTEN promotes apoptosis of H2O2‑injured rat nasal epithelial cells through PI3K/Akt and other pathways

“…PTEN can dephosphorylate PI(3,4,5)P3 to PI(4,5)P2 and PI (3,4)P2 to PI(4)P to switch off the pathway of promoting phosphorylation of Akt by PI3K, resulting in decreased p-Akt levels and negative regulation of the PI3K signaling pathway. Several lines of evidence support an antagonistic relationship between PTEN and Akt (22)(23)(24)(25)(26)(27). It was previously reported that membrane-associated guanylate kinases MAGI2 and MAGI3, which act upstream protein of PTEN, were able to enhance the activity of PTEN and inhibit the activity of Akt (23).…”

“…Hua et al found that p-Akt was highly expressed in prostate cancer cells when the PTEN gene was altered or inactivated (26). Bai et al demonstrated a reciprocal relationship between levels of PI3K/Akt and PTEN in gastric (27).…”

CDX2 Enhances HTR-8/SVneo Trophoblast Cell Invasion by Altering the Expression of Matrix Metalloproteinases

“…Literature also suggests that HCG stimulates trophoblast invasion through PI3K and AKT signaling [39]. Recent studies have shown that CDX-2 was a target of PI3K signaling [40,41]. We investigated the effect of PI3K/Akt signaling on CDX2 expression in HTR8/SVneo cells.…”