Effects of 17beta-estradiol and their receptors in cells of testicular cancer

• Grant number: 12/02362-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2012
• End date: February 28, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Catarina Segreti Porto
• Grantee: Thaís Fabiana Gameiro Lucas
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 08/56564-1 - Estrogen receptors: expression, regulation, signaling, and function in the male reproductive tract, breast, and brain, AP.TEM

Abstract

Testicular germ cell tumors type II are classified into two main categories: seminoma and nonseminoma (including embryonal carcinoma), both derived from common precursor cell type called carcinoma in situ. The dormancy period of these tumors until puberty suggests a hormone-dependent mechanism for development or progression of the tumor. Estrogen could play a role in this process. In seminoma and embryonal carcinoma, the presence of estrogen receptors ESR2 (ER²), but not ESR1 (ER±), was detected. In embryonal carcinoma cells NTERA-2 testicular cl.D1 (NT2/D1), the presence of both ESR1 and ESR2 was detected. In TCam-2 cells (seminoma), the presence of ESR1 was detected and the presence of ESR2 was not explored. The G-protein-coupled estrogen receptor (GPER) was detected in intratubular germ cell tumors, embryonal carcinoma, seminoma and in TCam-2 cells. In testicular cancer different genes and the deregulation of intracellular signaling pathways are involved. The transcription factor Krüppel-like factor 4 (KLF4) may play an important role in embryonic cells and in pluripotent stem cells. KLF4 is a transcription factor involved in many cellular and developmental processes such as terminal differentiation of cells and carcinogenesis. This factor was not detected in normal human testicular spermatogonia, but carcinoma in situ and seminoma expressed KLF4 at high levels in the nucleus, suggesting that KLF4 may play a critical role in the development and maintenance of carcinoma in situ and seminoma. If in testicular cancer the estrogen receptors, their signaling pathways and the expression and/or activation of KLF4 play a role, need to be further explored. The better understanding of the molecular mechanisms involved in the development and maintenance of these tumors may reveal new therapeutic targets for the treatment. The aim of the present study is to investigate the proliferative and/or anti-proliferative effects of 17²-estradiol and their receptors in TCam-2-(seminoma) and NT2/D1 (embryonal carcinoma) cells. The role of signaling pathways MEK-ERK1/2 and PI3K/AKT and the transcription factor KLF4 in these processes will be also evaluated.