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Gene expression profiling of the tumor fibroblasts in breast cancer classified into subtypes by estrogen and progestorone receptors and ERBB-2 status

Grant number: 09/10088-7
Support type:Research Projects - Thematic Grants
Duration: December 01, 2009 - November 30, 2013
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Maria Mitzi Brentani
Grantee:Maria Mitzi Brentani
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators:Dirce Maria Carraro ; Helena Paula Brentani ; Maria Aparecida Azevedo Koike Folgueira
Assoc. researchers: Cynthia Aparecida Bueno de Toledo Osorio ; Fabiana Baroni Alves Makdissi ; Maria Do Socorro Maciel ; Maria Lucia Hirata Katayama ; Patricia Bortman Rozenchan ; Rosimeire Aparecida Roela
Associated scholarship(s):11/08194-3 - Changes in the expression profile of microRNAs in fibroblasts associated with breast compared with those obtained from samples of normal breast tissue, BP.DR
11/06752-9 - Genetic and microRNAs patterns analysis to identify biomarker associated to aggressive behavior of breast carcinoma in young women, BP.DR

Abstract

Breast cancer is an heterogenous disease that can be classified into sutypes based in gene expression patterns including mainly a luminal group (ER+PR+erbB2-) and a basal like subtype (ER-PR-erbB2-, cytokeratin 5/6 positive) which were correlated with patient outcome. Stromal fibroblasts influence the behavior of breast carcinoma epithelial cells adding one more factor to this complex profile due to the effects derived of the heterotypic interactions between epithelium-stroma. Little is known regarding how molecular changes in the tumor stroma affect epithelial cells of the different subtypes of breast ductal breast carcinoma. Our first aim is to combine laser capture microdissection for isolation of tumor associated and paired normal stroma from breast carcinomas classified as luminal or basal with the Roche 454 deep sequence technology to obtain a comparative analysis of transcriptomes of both stromal types. In the subproject 2 we sought to identify microRNAs that are differentially expressed in associated tumor stroma of distinct breast tumor subtypes and correspondent normal fibroblasts. In the subproject number 3, we aimed to analyze the effects of vitamin D3 upon proliferation and changes in genomic profile of tumor associated fibroblasts or normal fibroblasts obtained by primary culture. The fourth subproject aims to analyze the tumor-stromal interactions in peripheral lymph-nodes of breast cancer. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
New target in the battle against breast cancer 
Articles published in Pesquisa FAPESP Magazine about the research grant:
Unexpected supporting actors 
Unexpected supporting actors 

Scientific publications (8)
(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)
HIRATA KATAYAMA, MARIA LUCIA; COSTA VIEIRA, RENE ALOISIO; ANDRADE, VICTOR PIANA; ROELA, ROSIMEIRE APARECIDA; CERNAGLIA AURELIANO LIMA, LUIZ GUILHERME; KERR, LIGIA MARIA; DE CAMPOS, ADRIANO POLPO; DE BRAGANCA PEREIRA, CARLOS ALBERTO; DE MENEZES PACHECO SERIO, PEDRO ADOLPHO; ENCINAS, GISELLY; MAISTRO, SIMONE; LEITE PETRONI, MATHEUS DE ALMEIDA; BRENTANI, MARIA MITZI; AZEVEDO KOIKE FOLGUEIRA, MARIA APARECIDA. Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer. CELLS, v. 8, n. 12 DEC 2019. Web of Science Citations: 0.
MUNDIM, FIORITA G. L.; PASINI, FATIMA S.; NONOGAKI, SUELY; ROCHA, RAFAEL M.; SOARES, FERNANDO A.; BRENTANI, MARIA M.; LOGULLO, ANGELA F. Breast Carcinoma-associated Fibroblasts Share Similar Biomarker Profiles in Matched Lymph Node Metastasis. APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY, v. 24, n. 10, p. 712-720, NOV-DEC 2016. Web of Science Citations: 3.
ROZENCHAN, PATRICIA BORTMAN; PASINI, FATIMA SOLANGE; ROELA, ROSIMEIRE A.; HIRATA KATAYAMA, MARIA LUCIA; LOPES MUNDIM, FIORITA GONZALES; BRENTANI, HELENA; LYRA, EDUARDO C.; BRENTANI, MARIA MITZI. Specific upregulation of RHOA and RAC1 in cancer-associated fibroblasts found at primary tumor and lymph node metastatic sites in breast cancer. TUMOR BIOLOGY, v. 36, n. 12, p. 9589-9597, DEC 2015. Web of Science Citations: 11.
LOPES MUNDIM, FIORITA GONZALES; PASINI, FATIMA SOLANGE; BRENTANI, MARIA MITZI; SOARES, FERNANDO AUGUSTO; NONOGAKI, SUELY; LOGULLO WAITZBERG, ANGELA FLAYIA. MYC is expressed in the stromal and epithelial cells of primary breast carcinoma and paired nodal metastases. MOLECULAR AND CLINICAL ONCOLOGY, v. 3, n. 3, p. 506-514, MAY 2015. Web of Science Citations: 0.
BASTOS, ELEN PEREIRA; BRENTANI, HELENA; PASINI, FATIMA SOLANGE; SILVA, ADERBAL RUY T.; TORRES, CESAR HENRIQUE; PUGA, RENATO DAVID; RIBEIRO OLIVIERI, ELOISA HELENA; PIOVEZANI, AMANDA RUSISKA; DE BRAGANCA PEREIRA, CARLOS ALBERTO; MACHADO-LIMA, ARIANE; CARRARO, DIRCE MARIA; BRENTANI, MARIA MITZI. MicroRNAs Discriminate Familial from Sporadic Non-BRCA1/2 Breast Carcinoma Arising in Patients <= 35 Years. PLoS One, v. 9, n. 7 JUL 9 2014. Web of Science Citations: 6.
GIORGI GROSSO, STANA HELENA; HIRATA KATAYAMA, MARIA LUCIA; ROELA, ROSIMEIRE APARECIDA; NONOGAKI, SUELY; SOARES, FERNANDO AUGUSTO; BRENTANI, HELENA; LIMA, LEANDRO; AZEVEDO KOIKE FOLGUEIRA, MARIA APARECIDA; LOGULLO WAITZBERG, ANGELA FLAVIA; PASINI, FAIMA SOLANGE; GUEDES SAMPAIO GOES, JOAO CARLOS; MITZI BRENTANI, M. Breast cancer tissue slices as a model for evaluation of response to rapamycin. Cell and Tissue Research, v. 352, n. 3, p. 671-684, JUN 2013. Web of Science Citations: 7.
MILANI, CINTIA; HIRATA KATAYAMA, MARIA LUCIA; DE LYRA, EDUARDO CARNEIRO; WELSH, JOELLEN; CAMPOS, LAURA TOJEIRO; MITZI BRENTANI, M.; MACIEL, MARIA DO SOCORRO; ROELA, ROSIMEIRE APARECIDA; DEL VALLE, PAULO ROBERTO; GUEDES SAMPAIO GOES, JOAO CARLOS; NONOGAKI, SUELY; TAMURA, RODRIGO ESAKI; AZEVEDO KOIKE FOLGUEIRA, MARIA APARECIDA. Transcriptional effects of 1,25 dihydroxyvitamin D-3 physiological and supra-physiological concentrations in breast cancer organotypic culture. BMC CANCER, v. 13, MAR 15 2013. Web of Science Citations: 20.
CARRARO, DIRCE MARIA; AZEVEDO KOIKE FOLGUEIRA, MARIA APARECIDA; GARCIA LISBOA, BIANCA CRISTINA; RIBEIRO OLIVIERI, ELOISA HELENA; VITORINO KREPISCHI, ANA CRISTINA; DE CARVALHO, ALEX FIORINI; DE CARVALHO MOTA, LOUISE DANIELLE; PUGA, RENATO DAVID; MACIEL, MARIA DO SOCORRO; DEPIERI MICHELLI, RODRIGO AUGUSTO; DE LYRA, EDUARDO CARNEIRO; GIORGI GROSSO, STANA HELENA; SOARES, FERNANDO AUGUSTO; DE SOUZA WADDINGTON ACHATZ, MARIA ISABEL ALVES; BRENTANI, HELENA; MOREIRA-FILHO, CARLOS ALBERTO; BRENTANI, MARIA MITZI. Comprehensive Analysis of BRCA1, BRCA2 and TP53 Germline Mutation and Tumor Characterization: A Portrait of Early-Onset Breast Cancer in Brazil. PLoS One, v. 8, n. 3 MAR 1 2013. Web of Science Citations: 40.

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