RETRACTED ARTICLE: Reducing PKCδ inhibits tumor growth through growth hormone by inhibiting PKA/CREB/ERK signaling pathway in pituitary adenoma

Abstract

Abstract Patients with growth hormone-secreting pituitary adenoma (GHPA) often fail to exhibit the molecular signatures typically associated with tumorigenesis. This study investigates the role of protein kinase C delta (PKCδ) in modulating cell apoptosis, migration, invasion, and tumor growth in pituitary adenoma. We assessed the activation of the PKA/CREB/ERK signaling pathway and cell apoptosis through RT-qPCR and western blot analysis. Wound-healing and transwell assays were employed to evaluate cell migration and invasion. Combined treatment with rottlerin and phorbol 12-myristate 13-acetate (PMA) reversed the inhibition of the PKA/CREB/ERK signaling pathway, downregulated cell apoptosis, and reduced growth hormone secretion in GH3 cells. A decrease in the level of PKCδ also inhibited the PKA/CREB/ERK signaling pathway, reduced cell apoptosis, and suppressed the secretion of growth hormone. Notably, growth hormone reversed the decline in cell migration and invasion following PKCδ siRNA treatment. Moreover, in nude mice with tumor models, growth hormone reversed the reduction in tumor volume induced by PKCδ siRNA. In conclusion, this study demonstrates that reducing PKCδ inhibits tumor growth by suppressing growth hormone via inhibition of the PKA/CREB/ERK signaling pathway.

Keywords

• Protein kinase Cδ
• PKA/CREB/ERK signaling pathway
• Growth hormone
• Tumor growth
• Apoptosis