EZH2 AS A TARGET OF PROGESTERONE RECEPTOR-MEDIATED BREAST CANCER GROWTH

MAURO E CENCIARINI; MATIAS AMASINO; MARIA FLORENCIA CHERVO; MARA DE MARTINO; VIOLETA CHIAUZZI; YANMING WU; KEXIN XU; FELIPE GUSTAVO GERCOVICH; ERNESTO GIL DEZA; SANDRA ARES; ROXANA SCHILLACI; PATRICIA V ELIZALDE; CECILIA J PROIETTI

Congreso; LXII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2017

On the basis of Estrogen Receptor (ER) presence, breast cancer(BC) patients are treated with selective ER modulators (SERMs)such as tamoxifen. However, approximately 40% of women receivingTAM experience tumor relapse. We and others have previouslyreported Progesterone Receptor (PR) participation in BC growth.We therefore propose that, being blocked ER, PR may take controlof tumor growth, progression and endocrine resistance. We havedescribed that the progestin medroxiprogesterone acetate (MPA)induces the interaction between PR and EZH2 to promote transcriptionalrepression of tumor suppressor GATA3. EZH2, a histonemethyltransferase, is often overexpressed in different types of cancersand associated with poor overall survival. The objective of thiswork was to study the role of EZH2 in MPA-induced BC growth. Invitro studies were carried out in the T47D human BC cell line andin primary cultures of the MPA-dependent C4HD tumor. Firstly, MPA(10 nM) induced EZH2 expression after 18 and 24 h of treatment,seen by increased levels of both mRNA (qPCR, p