p38β - MAPK11 and its role in female cancers

Abstract

Background The p38MAPK family of Mitogen Activated Protein Kinases are a group of signalling molecules involved in cell growth, survival, proliferation and differentiation. The widely studied p38α isoform is ubiquitously expressed and is implicated in a number of cancer pathologies, as are p38γ and p38δ. However, the mechanistic role of the isoform, p38β, remains fairly elusive. Recent studies suggest a possible role of p38β in both breast and endometrial cancer with research suggesting involvement in bone metastasis and cancer cell survival. Female tissue specific cancers such as breast, endometrial, uterine and ovary account for over 3,000,000 cancer related incidents annually; advancements in therapeutics and treatment however require a deeper understanding of the molecular aetiology associated with these diseases. This study provides an overview of the MAPK signalling molecule p38β (MAPK11) in female cancers using an in-silico approach. Methods A detailed gene expression and methylation analysis was performed using datasets from cBioportal, CanSar and MEXPRESS. Breast, Uterine Endometrial, Cervical, Ovarian and Uterine Carcinosarcoma TCGA cancer datasets were used and analysed. Results Data using cBioportal and CanSAR suggest that expression of p38β is lower in cancers: BRCA, UCEC, UCS, CESC and OV compared to normal tissue. Methylation data from SMART and MEXPRESS indicate significant probe level variation of CpG island methylation status of the gene MAPK11. Analysis of the genes’ two CpG islands shows that the gene was hypermethylated in the CpG1 with increased methylation seen in BRCA, CESC and UCEC cancer data sets with a slight increase of expression recorded in cancer samples. CpG2 exhibited hypomethylation with no significant difference between samples and high levels of expression. Further analysis from MEXPRESS revealed no significance between probe methylation and altered levels of expression. In addition, no difference in the expression of BRCA oestrogen/progesterone/HER2 status was seen. Conclusion This data provides an overview of the expression of p38β in female tissue specific cancers, showing a decrease in expression of the gene in BRCA, UCEC, CESC, UCS and OV, increasing the understanding of p38β MAPK expression and offering insight for future in-vitro investigation and therapeutic application.

Functional Roles of JNK and p38 MAPK Signaling in Nasopharyngeal Carcinoma

“…In addition, different isoforms of p38 MAPK can specifically activate different kinds of downstream molecules depending on their substrate specificity. For instance, p38α, p38β, and p38γ activate MAPK-activated protein (MAPKAP-2 or MK2) and heat shock protein 27 (HSP27), while p38δ activates eukaryotic elongation factor 2 kinase (eEF2K) [35][36][37][38]. These proteins will ultimately lead to regulation of gene expression, cell motility, transcription, and chromatin remodeling (Figure 3) [19].…”

Differential Regulation of Genes by the Glucogenic Hormone Asprosin in Ovarian Cancer

“…Following treatment with 100 nM asprosin, the SKOV-3 model did not demonstrate any change in Akt phosphorylation, 5 or 15 min after asprosin was administered. Nor were there marked changes for p38, an integral molecule involved in cell death which is associated with female cancers [ 70 ]. Our data does, however, indicate a short-lived increase in the phosphorylation of ERK 1/2, 5 min after asprosin treatment ( Figure 7 ).…”

p38 mitogen‐activated protein kinase: Functions and targeted therapy in diseases

“…72 Recent studies have detected elevated levels of p38β in a variety of female cancers, including breast cancer and endometrial cancer, suggesting that p38β may play a potential role. 73 P38γ modulates gamma radiation-induced G2 phase arrest. 74 In addition, p38γ acts as a CDK kinase, synergistic with CDK to regulate the G0 to G1 transition into the cell cycle.…”