Efeitos iniciais da superexpressão de SOX2 sobre queratina-19 e integrina α2β1 em células MCF-7: análise morfológica e molecular de transição fenotípica

Abstract

Breast cancer is a heterogeneous disease, highly incident and lethal worldwide. The main cause for death related to mammary neoplasia is the progression of the lesion, which leads to metastasis. Although being efficient when conducted in early stages, the treatment against breast cancer is not always successful, as many cases of re-incidence and resistance against chemotherapy are registered. One of the reasons for this is the plurality of cases between patients, and the difficulty on finding a universal therapy. There are four main molecular subtypes of breast cancer, which are differently aggressive between each other; the subtypes luminal A and B, the least aggressive; the HER2+ subtype; and the triple negative, the most aggressive. In light of this, investigating initial mechanisms of breast cancer formation might reveal insights to the comprehension of genetical and morphological changes faced by tumoral cells in the oncogenic process in vivo. In this sense, this work aimed to comprehend the functioning of the transcription factor SOX2, a regulator of pluripotency, differentiation, apoptosis and pro-tumoral signaling pathways in a model of transfection and overexpression of SOX2 in MCF-7 cell line, which is a model of study for the luminal A molecular subtype. It was observed that early molecular and morphological changes occurred in a time span of 24h. These cells, that traditionally present epithelial phenotype underwent changes towards a fusiform morphology, presenting loss of differentiation and decrease on cytokeratin 19 and F-actin levels, cytoskeletal proteins. Besides this, the well-studied promoter of metastasis and integrin β1 presented higher levels in cells overexpressing SOX2. However, these molecular changes are not evenly paced, as integrins levels increases before the decrease of cytokeratin and actin. This leads to the suggestion that SOX2-overexpressing MCF-7 cells commit earlier to adhesion and protrusion formation, in order to acquire mobility, to then initiate the process of cytoskeletal changes that will lead to increased plasticity and malleability, necessary for matrix traffic. This work concludes that overexpression of SOX2 reduces keratin 19 and F-actin levels, anteceded by increase on integrin β1 levels, changes that are compatible with characteristics of increased aggressiveness and lesser differentiation, which could serve as platform for new studies directed to oncogenesis of MCF-7 cells.