Advanced search
Start date
Betweenand

Study of epigenetic regulation of transcription factor POD-1/TCF21in adrenocortical tumor cell cultures and its role in the cellular migration and invasion

Grant number: 16/17285-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2017
Effective date (End): September 30, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Claudimara Ferini Pacicco Lotfi
Grantee:Jean Lucas Kremer
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Adrenocortical tumors are common findings in adults most of which are adenomas, the treatment consists of clinical and radiological observation. On the other hand, the carcinomas are rare and with limited prognosis, whose treatment is surgical. However, some have metastases and adjuvant therapies are only palliative. There is an interest in the study of the adrenal cortex tumors since its incidence in Brazil is about 10 to 15 times higher than the rest of the world. Microarray results showed that the POD1 expression is diminished in carcinomas than adenomas and normal adrenal. Studies in our group have shown that increasing expression of POD1 in adrenocortical carcinoma cells decreased the expression of SF-1 after binding in the E-box site of its promoter and decreased the expression of steroidogenic enzymes. SF-1 is amplified and overexpressed in adrenocortical tumors adult and pediatric, and other tumors such as melanoma, lung cancer, kidney, bladder and prostate POD1 is epigenetically silenced. In melanomas, the lowest expression of POD1 is related to the increase in cell invasiveness and metastasis, and when it is overexpressed there is an increase of the expression of tumor suppressor KISS1 and reduced migration capability. Preliminary results from our laboratory have shown that mouse adrenocortical carcinoma line cells, Y1 cells, transfected with pcDNA3Pod1 vector, showed decreased migration capability. However, we are not known the molecular mechanisms that regulate the migration and invasion, and whether these phenomena depend on the methylation state of POD1 gene in human adrenocortical tumors. However, the loss or decreased expression of POD1 gene has been found in different types of cancers due to hypermethylation of its promoter. However, the study of epigenetic regulation by methylation and the molecular function of POD1 gene in adrenocortical is incipient. Thus, in this project we propose to examine the condition of methylation of POD1 promoter in different cultures of adrenocortical tumor cells lines and tumor cell culture from patients obtained in our laboratory, and to analyze the migration capability and invasion POD1 by overexpression of POD1 in tumor cells. In addition, we will analyze the promoter methylation status of POD1 adrenocortical adenomas and carcinomas of patients. In addition, we will examine the migration and MET/EMT mechanisms by analyzing the expression of molecular factors related to these phenomena. Therefore, our hypothesis is that POD1 is a transcription factor and a tumor suppressor gene by inhibiting the migration / adrenocortical tumor cell invasion, and with a role in tumor progression due the control of methylation of POD1 promotor condition.

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)
PASSAIA, BARBARA DOS SANTOS; LIMA, KELI; KREMER, JEAN LUCAS; DA CONCEICAO, BARBARA BRITO; DE PAULA MARIANI, BEATRIZ MARINHO; LIPRERI DA SILVA, JEAN CARLOS; NOGUEIRA ZERBINI, MARIA CLAUDIA; BARISSON VILLARES FRAGOSO, MARIA CANDIDA; MACHADO-NETO, JOAO AGOSTINHO; PACICCO LOTFI, CLAUDIMARA FERINI. Stathmin 1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours. INVESTIGATIONAL NEW DRUGS, v. 38, n. 3, p. 899-908, JUN 2020. Web of Science Citations: 0.
CLAUDIMARA FERINI PACICCO LOTFI; JEAN LUCAS KREMER; BARBARA DOS SANTOS PASSAIA; ISADORA PONTES CAVALCANTE. The human adrenal cortex: growth control and disorders. Clinics, v. 73, p. -, 2018.
PACICCO LOTFI, CLAUDIMARA FERINI; KREMER, JEAN LUCAS; PASSAIA, BARBARA DOS SANTOS; CAVALCANTE, ISADORA PONTES. The human adrenal cortex: growth control and disorders. Clinics, v. 73, n. 1 2018. Web of Science Citations: 2.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.