Identification of an AP1-ZFP36 Regulatory Network Associated with Breast Cancer Prognosis
| Autor: | Julian Naipauer, Martín Carlos Abba, Edith C. Kordon, Norberto Ariel Gandini, Maria Marta Facchinetti, Romina Canzoneri, A. Rodriguez Peña, Micaela Nadia Stedile, Ezequiel Lacunza, Alejandro Carlos Curino, Omar A. Coso |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research CIENCIAS MÉDICAS Y DE LA SALUD TTP JUNB Biología Mammary gland Breast Neoplasms Biology BREAST 03 medical and health sciences 0302 clinical medicine Breast cancer Tristetraprolin TUMOR medicine Biomarkers Tumor ZFP36 Humans Gene Regulatory Networks Breast STAT5 BTG2 Cancer Computational Biology Bioquímica y Biología Molecular medicine.disease Prognosis AP-1 CANCER Gene Expression Regulation Neoplastic Transcription Factor AP-1 AP-1 transcription factor Medicina Básica 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Ciencias Médicas Cancer research biology.protein Female FOSB |
| Zdroj: | SEDICI (UNLP) Universidad Nacional de La Plata instacron:UNLP |
| Popis: | It has been established that ZFP36 (also known as Tristetraprolin or TTP) promotes mRNA degradation of proteins involved in inflammation, proliferation and tumor invasiveness. In mammary epithelial cells ZFP36 expression is induced by STAT5 activation during lactogenesis, while in breast cancer ZFP36 expression is associated with lower grade and better prognosis. Here, we show that the AP-1 transcription factor components, i.e. JUN, JUNB, FOS, FOSB, in addition to DUSP1, EGR1, NR4A1, IER2 and BTG2, behave as a conserved co-regulated group of genes whose expression is associated to ZFP36 in cancer cells. In fact, a significant down-modulation of this gene network is observed in breast, liver, lung, kidney, and thyroid carcinomas compared to their normal counterparts. In breast cancer, the normal-like and Luminal A, show the highest expression of the ZFP36 gene network among the other intrinsic subtypes and patients with low expression of these genes display poor prognosis. It is also proposed that AP-1 regulates ZFP36 expression through responsive elements detected in the promoter region of this gene. Culture assays show that AP-1 activity induces ZFP36 expression in mammary cells in response to prolactin (PRL) treatment thorough ERK1/2 activation. These results suggest that JUN, JUNB, FOS and FOSB are not only co-expressed, but would also play a relevant role in regulating ZFP36 expression in mammary epithelial cells. Centro de Investigaciones Inmunológicas Básicas y Aplicadas |
| Databáze: | OpenAIRE |
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