Molecular characterization of abnormal mammary glands in transgenic mice carrying additional isoform A of progesterone receptor

• Grant number: 14/13470-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2015
• End date: April 30, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Maria Aparecida Nagai
• Grantee: Maria Jose Carlini
• Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The ovarian steroid hormones progesterone and estrogen play vital roles in the development of normal mammary gland and are likewise linked to mammary carcinogenesis via their receptors. Progesterone receptor (PR) is expressed as two isoforms, PR-A and PR-B. In human breast tumors the PR-A/PR-B expression ratio is altered, with the PR-A isoform predominating. Transgenic mice carrying an additional A form of PR (PR-A transgenics) have abnormal mammary gland development. Several characteristics of these mammary hyperplasias are compatible with mammary epithelial cell transformation and the phenomenom of epithelial-to-mesenchymal transition (EMT); which might in turn affect the stem cell population in the mammary gland. In this context, we will conduct a comprehensive analysis on various molecular levels in mammary lesions of transgenic mice with over-expression of PRA using gene expression analysis by RNAseq, large-scale analysis of DNA methylation, and microarray based high resolution comparative genomic hybridization (aCGH).As a result, an unprecedented detailed picture of the transcriptome, methylome, and genomic profile associated with the expression of PRA and the development of hyperplasia in the mammary gland will be described. This will represent not only a valuable information resource with which to identify novel signaling paradigms for mammary PR action, but also a potential tool for the formulation of useful molecular descriptors for diagnosis, prognosis, and/or therapy of breast cancer. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CARLINI, MARIA JOSE; RECOUVREUX, MARIA SOL; SIMIAN, MARINA; NAGAI, MARIA APARECIDA. Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands. BMC CANCER, v. 18, JUN 25 2018. (14/13470-8, 15/10208-3)