Caracterização fenotípica e genômica de duas linhagens de câncer de mama brasileiras derivadas de tumores primários humanos

Abstract

Breast cancer is the most common cancer among women worldwide. Research using breast cancer cell lines derived from primary tumors could add valuable knowledge about this type of cancer. The aim of this study was to investigate the genomic and phenotypic profiles of MACL-1 and MGSO-3 cell lines, derived from primary human tumors. The presence of hormone receptors, proliferation, differentiation, and stem cell markers were evaluated using immunohistochemistry of the primary tumor, cultured cells, and xenografts implanted in immunodeficient mice. The chromosomic profile and copy number alterations on these cells were investigated by G banding and array comparative genomic hybridization. To assess gene expression profile cDNA microarrays and Real time PCR were used. Histopathological analysis and immunohistochemistry showed that the invasive primary tumor from which MACL-1 cell line was derived was a luminal A subtype carcinoma, and the ductal carcinoma in situ that gave rise to MGSO-3 cell line was a HER2 subtype tumor. Cell lines and the xenograft tumors in mice preserved their high proliferative potential, but did not maintain the expression of all other markers investigated. Whole-genome evaluation showed a large amount of chromosome rearragements and copy number alterations in both cell lines, especially losses. The preliminary analysis of cDNA microarray data exhibits main changes on different cell signaling pathways and Real time PCR analysis confirmed the expression level of some of the genes from the microarray. These findings make MACL-1 and MGSO-3 the first characterized Brazilian breast cancer cell lines, which could be potentially used for comparative research.