title: The interplay between intracellular progesterone receptor and PKC plays a key role in migration and invasion of human glioblastoma cells.
abstract: 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.
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Programa de Investigación en Cancer de Mama, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
authors.forename: Brenda
authors.initials: B
authors.lastname: Marquina-Sánchez
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Programa de Investigación en Cancer de Mama, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
authors.forename: Jesús
authors.initials: J
authors.lastname: González-Jorge
authors.affiliation: Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de México, Mexico.
authors.forename: Valeria
authors.initials: V
authors.lastname: Hansberg-Pastor
authors.affiliation: Dirección de Investigación, Instituto Nacional Cancerología, Ciudad de México, Mexico.
authors.forename: Talia
authors.initials: T
authors.lastname: Wegman-Ostrosky
authors.affiliation: División de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México 14080, Mexico.
authors.forename: Noemi
authors.initials: N
authors.lastname: Baranda-Ávila
authors.affiliation: Subdirección de Neurocirugía, Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, Mexico.
authors.forename: Sonia
authors.initials: S
authors.lastname: Mejía-Pérez
authors.affiliation: Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico. Electronic address: camachoarroyo@gmail.com.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Camacho-Arroyo
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Programa de Investigación en Cancer de Mama, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico. Electronic address: alieshagonzalez@gmail.com.
authors.forename: Aliesha
authors.initials: A
authors.lastname: González-Arenas
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000235:genetics* / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000235:genetics* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013491:Suppressor Factors, Immunologic / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D006727:Hormone Antagonists; C110058:PIBF1 protein, human; D011257:Pregnancy Proteins; D011980:Receptors, Progesterone; D013491:Suppressor Factors, Immunologic; D015735:Mifepristone; C496628:PRKCA protein, human; C497258:PRKCD protein, human; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D013755:Tetradecanoylphorbol Acetate
keywords: Glioblastoma; Invasion; Migration; PIBF; PKCα; Progesterone receptor