title: PTEN expression and suppression of proliferation are associated with Cdx2 overexpression in gastric cancer cells.
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.
authors.affiliation: Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Bai
authors.forename: Ying-Jiang
authors.initials: YJ
authors.lastname: Ye
authors.forename: Dan-Hua
authors.initials: DH
authors.lastname: Shen
authors.forename: You-Yong
authors.initials: YY
authors.lastname: Lu
authors.forename: Zhong-Tao
authors.initials: ZT
authors.lastname: Zhang
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000071616:CDX2 Transcription Factor; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D005774:Gastrostomy; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human