Estradiol regulates the expression and subcellular localization of filamin a in the pituitary tumoral development

PEREZ PABLO ANÍBAL; MUKDSI JORGE HUMBERTO; MASINI AGUSTINA; DE PAUL ANA LUCIA; TOLEDO JONATHAN; MOYANO CRESPO GABRIELA; GUTIÉRREZ SILVINA

Cordoba

Jornada; XIX Jornada de la Facultad de Ciencias Medicas (JIC); 2018

FCM, UNC

Estrogens regulate the pituitary cell proliferation. The prolactinomes are more frequent in women and increase in size during pregnancy or estrogen treatment. Nevertheless, the mechanisms involved remain to be elucidated. In relation to this, the present study proposes to analyze if E2 regulates the expression and subcellular localization of Filamin A (FLNA), a potential oncogenic protein, capable to promote or inhibit tumoral growth and development.In order to reach this objective, a murine tumor pituitary model induced by chronic administration of E2 was used. Anterior pituitary glands were extracted and processed for the determination of primary transcripts by RNA sequencing, FLNA expression and subcellular localization by confocal and electron microscopy, expression of cell cycle regulatory proteins by Western Blot, and DNA content by Flow Cytometry. A Statistical analysis ANOVA-Tukey was used.The results showed that E2 chronic stimulation triplicated the levels of FLNA transcripts. Also, it has been observed an increase of this protein in nuclear and cytoplasmic localization during the pituitary tumor development, with a strong nucleolar signal. These changes were associated with a significant upregulation of cyclin D1 and CDK4 expression during the tumor development, with a significant increase in the number of cells in the proliferative phase (S + G2/M).These observations suggest that E2 modulates genetic expression of FLNA and induces it subcellular redistribution as part of the mechanisms involved in the experimental pituitary tumor development.