Title : Effect of BRCA silence on the nervous system in a murine model of breast cancer
Abstract:
Cancer is a complex pathology of great relevance for public health due to its high mortality and morbidity. Specifically breast cancer, is one of the main causes of death in women worldwide, demonstrating that its incidence has been exponentially uprising. The multifactorial nature of breast cancer makes it complex to address it; however, understanding its pathophysiological mechanisms and the factors involved in its development and progression is key to enhancing early diagnostic tools, improving treatment alternatives and providing better strategies for managing long-term effects that diminish quality of life for those affected from it in a timely manner. These efforts to elucidate cancer’s mechanisms have identified genetics and the nervous system as relevant factors in understanding cancer behavior. Genetic alterations affecting genes crucial for maintaining homeostasis across bodily systems have been associated with an increased risk of certain types of cancer. This is the case of the BRCA gene, which under normal conditions, supports the development and proper functioning of the nervous system, however, when it is mutated, it predisposes to the development of breast, ovarian and pancreatic cancer, among others. In recent years, the nervous system’s role as a key factor for cancer development and proliferation has been increasingly recognized, with bidirectional interactions influencing cancer progression, metastasis, and prognosis. While these factors have been studied individually, considering cancer’s multifactorial nature, it is essential to investigate the combined effects of genetic and nervous system interactions in cancer patients. Thus, our objective in the present work is to evaluate the effect of BRCA gene silencing in the tumor on the nervous system using a murine model of breast cancer. To achieve this, we will first work on the 4T1 cell line, applying RNA interference to silence the BRCA gene and then evaluating its effect on BRCA gene expression using PCR technique. Subsequently, a murine model of breast cancer will be established and the interference RNA will be administered. After silencing, cognitive damage will be assessed through a battery of standardized ethological tests that will consider the dimensions of learning and memory, exploration, sensory skills, motor skills and anxiety. Following testing, the animals will then be euthanized in compliance with the applicable regulations, and histopathological lesions in the nervous system will be analyzed. Additionally, we will analyze the expression of neurodegeneration and neuroinflammation indicators using the immunohistochemistry technique. With the results obtained, we aim to generate insights that could led to the development of targeted therapies and improved palliative care options for patients with this disease.
