Trastuzumab inhibits pituitary tumor growth modulating the TGFB/Smad2/3 pathway

PETITI, JUAN PABLO; SOSA, LILIANA DEL VALLE; PICECH, FLORENCIA; MOYANO CRESPO, GABRIELA DEISI; AREVALO ROJAS, JEAN ZANDER; PÉREZ, PABLO ANIBAL; GUIDO, CAROLINA BEATRIZ; LEIMGRUBER, CAROLINA; SABATINO, MARÍA EUGENIA; GARCÍA, PEDRO EMILIO; BENGIÓ, VERÓNICA; PAPALINI, FRANCISCO ROQUE; ESTARIO, PAULA; BERNHARDT, MARIA CELINA; VILLARREAL, MARCOS; GUTIÉRREZ, SILVINA; DE PAUL, ANA LUCÍA; MUKDSI, JORGE HUMBERTO; TORRES, ALICIA I

ENDOCRINE - RELATED CANCER

BIOSCIENTIFICA LTD

Año: 2018

1351-0088

n pituitary adenomas, early recurrences and resistance to conventional pharmacotherapies are common, but the mechanisms involved are still not understood. The high expression of epidermal growth factor receptor 2 (HER2)/extracellular signal-regulated kinase (ERK1/2) signal observed in human pituitary adenomas, together with the low levels of the antimitogenic transforming growth factor beta receptor 2 (TBR2), encouraged us to evaluate the effect of the specific HER2 inhibition with trastuzumab on experimental pituitary tumor cell growth and its effect on the antiproliferative response to TGFB1. Trastuzumab decreased the pituitary tumor growth as well as the expression of ERK1/2 and the cell cycle regulators cyclin D1 and CDK4. The HER2/ERK1/2 pathway is an attractive therapeutic target, but its intricate relations with other signaling modulators sti