Expression level of Pre B cell leukemia homeobox 2 correlates with poor prognosis of gastric adenocarcinoma and esophageal squamous cell carcinoma

Abstract

Abstract. Pre B cell leukemia homeobox 2 (PBX2), a member of PBX family, acts as a co-factor of homeobox proteins to regulate proliferation and differentiation of tumor cells. Our recent study revealed prognostic significance of PBX2 expression in non-small cell lung carcinoma. The significance of PBX2 expression was examined in cases with gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC), and the role of PBX2 in tumor behavior was evaluated in GC and ESCC cell lines of knocked-down PBX2 expression. Expression level of PBX2 was immunohistochemically examined in 94 patients of GC and 64 patients of ESCC. Staining intensity for PBX2 was categorized as equal to or stronger (level 1) and weaker (level 2) than that of endothelial cells. Cases with level 1 expression in more than 20% of tumor were defined as high and others low expression. Patients with low PBX2 expression showed a better prognosis than those with high expression in both GC and ESCC. Multivariate analysis revealed PBX2 expression to be an independent prognosticator for both GC and ESCC. Knocked-down expression of PBX2 in GC and ESCC cell lines resulted in decrease of in vitro colony formation and in vivo tumorigenic activities, but proliferative and invasive activities did not change. Under serum depletion, apoptotic cell proportion was higher in PBX2 knocked-down cells than in control cells. The knock-down of PBX2 reduced Bcl-2 expression. Taken together, the high expression level of PBX2 was an independent negative prognosticator for both GC and ESCC, and PBX2 might promote tumor growth through suppression of apoptosis.

Identification of new therapeutic targets inCRLF2-overexpressing B-ALL through discovery of TF-gene regulatory interactions

“…It has also been shown to work as a cofactor with the HOXA9 protein 75 . Knockdown of PBX2 leads to increased apoptosis in adenocarcinoma and esophageal squamous cell carcinoma cancer cell lines 76 . PBX2 is also an inferred regulator of the down-regulated PTPN7 gene in CRLF2 -overexpressing patients and cell lines.…”

Oncogenic miR-146a-PBX2 axis, a novel leukemic target in xenograft acute lymphoblastic leukemia model

“…The increased expression level of PBX2 gene is correlated with poor prognosis in lung and gastric cancer (Jianjiao Lin et al, 2021). Overly expressed PBX2 gene activates BCL-2, an anti-apoptotic gene, suggesting PBX2 may be involved in cancer initiation and progression (Blackwell et al, 2009;Qiu et al, 2010Qiu et al, , 2012. According to the in silico analysis, PBX2 gene upregulates c-Myc, a pro-oncogene which is a potent regulator of hematopoiesis.…”