The interplay between intracellular progesterone receptor and PKC plays a key role in migration and invasion of human glioblastoma cells

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 172; pp. 198 - 206
• Main Authors: Marquina-Sánchez, Brenda, González-Jorge, Jesús, Hansberg-Pastor, Valeria, Wegman-Ostrosky, Talia, Baranda-Ávila, Noemi, Mejía-Pérez, Sonia, Camacho-Arroyo, Ignacio, González-Arenas, Aliesha
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2017; Elsevier BV
• Subjects: 12-O-Tetradecanoylphorbol-13-acetate; Acetic acid; Astrocytoma; Brain cancer; Brain tumors; Cancer; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Enzymes; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioblastoma cells; Hormone Antagonists - pharmacology; Humans; Intracellular; Invasion; Isoenzymes; Isoforms; Metastases; Metastasis; Mifepristone - pharmacology; Migration; Neuroglia - drug effects; Neuroglia - metabolism; Neuroglia - pathology; PIBF; PKCα; Pregnancy Proteins - genetics; Pregnancy Proteins - metabolism; Progesterone; Progesterone receptor; Progesterone receptors; Protein kinase C; Protein Kinase C-alpha - genetics; Protein Kinase C-alpha - metabolism; Protein Kinase C-delta - genetics; Protein Kinase C-delta - metabolism; Receptors, Progesterone - antagonists & inhibitors; Receptors, Progesterone - genetics; Receptors, Progesterone - metabolism; Signal Transduction; Suppressor Factors, Immunologic - genetics; Suppressor Factors, Immunologic - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Transcription; PIBF; Progesterone receptor; PKCα; Migration; Invasion; Glioblastoma
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2016.10.001

•PR participates in migration and invasion of glioblastoma cells via PKC.•There is a cross-talk between PKC and PR in human glioblastoma progression.•The activation of PKCα and PKCδ induces PR transcriptional activity. Intracellular progesterone receptors (PRs) and protein kinases C (PKCs) are known regulators of cancer cell proliferation and metastasis. Both PRs and PKCs are found overexpressed in grade IV human astrocytomas, also known as glioblastomas, which are the most frequent and aggressive brain tumors. In the present study, we investigated whether PR activation by PKC induces the migration and invasion of glioblastoma derived cell lines and if PKCα and δ isoforms are involved in PR activation. We observed that PKC activation with tetradecanoylphorbol acetate (TPA) increases the migration and invasion capacity of two human glioblastoma derived human cell lines (U251 MG and U87) and that the treatment with the PR receptor antagonist RU486 blocks these processes. Interestingly, the pharmacological inhibition of the isoenzymes PKCα and PKCδ also resulted in a blocked PR transcriptional activity. Also, TPA-dependent PR activation increases the expression of progesterone-induced blocking factor (PIBF), a known PR target gene. These results hint to an existing cross-talk between PKCs and PRs in regulating the infiltration process of human glioblastomas.