Clinicopathological significance of p38β, p38γ, and p38δ and its biological roles in esophageal squamous cell carcinoma

Abstract

P38β, p38γ, and p38δ have been sporadically and scarcely reported to be involved in the carcinogenesis of cancers, compared with p38α isoform. However, little has been known regarding their clinicopathological significance and biological roles in esophageal squamous cell carcinoma (ESCC). Expression status of p38β, p38γ, and p38δ was assayed using immunohistochemistry with ESCC tissue microarray; ensuing clinicopathological significance was statistically analyzed. To define its biological roles on proliferation, migration and invasion of ESCC cell line Eca109 in vitro, MTT, wound healing, and Transwell assays were employed, respectively. As confirmation, athymic nude mice were taken to verify the effect over proliferation in vivo. It was found that both p38β and p38δ expression, other than p38γ, were significantly higher in ESCC tissues compared with paired normal controls. In terms of prognosis, only p38β expression was observed to be significantly associated with overall prognosis. Clinicopathologically, there was significant association between p38γ expression and clinical stage, lymph nodes metastases, and tumor volume. No significant association was found for p38β and p38δ between its expression and other clinicopathological parameters other than significant difference of expression between ESCC versus normal control. In Eca109, it was observed that p38β, p38γ, and p38δ can promote the cell growth and motility. As verification, over-expression of p38δ can promote, whereas knockdown of p38γ can prevent, the tumorigenesis in nude mice model xenografted with Eca109 cells whose basal level of p38δ was stably over-expressed and p38γ was stably knocked down. Together, our results demonstrate that p38β, p38γ, and p38δ played oncogenic roles in ESCC.

Multi-Kinase Inhibitor with Anti-p38γ Activity in Cutaneous T-Cell Lymphoma

“…Several studies have identified p38g inhibitors as promising therapeutic agents for many tumor types; such as colon (Yin et al, 2015), prostate (Browne et al, 2016), esophageal (Zheng et al, 2016), and breast cancers (Qi et al, 2015). In addition to activity against CTCL, the p38g inhibitor we identified, F7/PIK75, also shows activity against cells derived from several types of cancers, including prostate, ovarian, and breast cancers (see Supplementary Table S2).…”

Partition-Defective 3 (PARD3) Regulates Proliferation, Apoptosis, Migration, and Invasion in Esophageal Squamous Cell Carcinoma Cells

“…MTT (Sigma-Aldrich, St Louis, MO, USA) was used to measure cell proliferation [16]. Cells were incubated in 20 μL of MTT at 37°C for 4 h. The color was developed by incubating the cells in 150 μL of dimethyl sulfoxide (DMSO), and the absorbance was measured at 490 nm.…”

The Role of p38γ in Cancer: From review to outlook

“…In the case of esophageal squamous cell carcinoma (ESCC), stable down-regulation of p38γ can prevent tumorigenesis in a nude mouse model of ESCC cell xenotransplantation [49]. In addition, p38γ can promote the movement and proliferation, and prevent the apoptosis of ESCC cells in vitro [49]. Similarly, higher p38γ expression is also observed in head and neck squamous cell carcinoma cells [20].…”

“…Literatures have demonstrated the value of p38γ in diagnosis. For example, researchers use immunohistochemistry with tissue microarray and performed a statistical analysis of its clinicopathological significance [49]. The expression of p38γ in ESCC is significantly different between clinical stage (P = 0.017), lymph node metastasis (P = 0.008) and tumor volume (P = 0.017) [49].…”

“…For example, researchers use immunohistochemistry with tissue microarray and performed a statistical analysis of its clinicopathological significance [49]. The expression of p38γ in ESCC is significantly different between clinical stage (P = 0.017), lymph node metastasis (P = 0.008) and tumor volume (P = 0.017) [49]. In terms of prognosis, no conspicuous discrepancy is observed between patients with different levels of p38γ expression (P = 0.667) in ESCC [49].…”