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Study to evaluate the crosstalk between estrogens and growth factors pathways on the transcriptional regulation of HNRPK, PAWR and PHLDA1.

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Author(s):
Simone Aparecida de Bessa Garcia
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Maria Aparecida Nagai; Maria Aparecida Azevedo Koike Folgueira; Durvanei Augusto Maria; Carlos Alberto Moreira Filho; Shigueko Sonohara Troyano Pueyo
Advisor: Maria Aparecida Nagai
Abstract

The crosstalk between estrogens and growth factors pathways has been associated with breast cancer aggressiveness. Based on this, the present study aimed to determine the possible crosstalk between E2 and EGF pathways on the HNRPK, PAWR and PHLDA1 expression regulation in MCF-7 (ER+) and MDA-MB-231 (ER-) cells. In MCF-7 cells, treatments with E2 and EGF decreased PAWR expression and increased PHLDA1 expression. The ER inhibition by the ICI treatment resulted in increased PAWR expression. The E2 or EGF addition down-regulated its expression without a return to the levels observed after the E2 or EGF treatments alone. To the PHLDA1 gene, the effect of E2 and EGF treatments did not change after the ICI treatment. In MDA-MB-231 cells, the EGF effect was more significant on the PAWR gene expression control. The ERK1/2 pathway is important to the ER activation by EGF. The EGF effect over the PHLDA1 is dependent on the ERK1/2 and p38 MAPK activation. These findings suggest a crosstalk between E2 and EGF pathways on the PAWR expression control but not to PHLDA1. (AU)