Evaluation of Bax and Bak Gene Mutations and Expression in Breast Cancer

Abstract

Genetic analyses have provided evidence to suggest that Bax and Bak are the essential genes for apoptosis in mammalians cells. This study aimed to search for biomarkers in breast cancer to be used as prognostic markers for the disease. The Bak and Bax genes expressions were analyzed in 23 breast cancer patients by RT-PCR technique. SSCP technique was used to detect the mobility of the abnormal fragment in Bak exon 4. PCR for Bax promoter was digested with Tau 1 restriction enzyme to identify a single polymorphism G(-248)A. The expression of Bak gene is related to several clinical factors of breast cancer. The analysis of Bax RNA showed 4 isoforms of Bax with different distributions in the normal and tumor tissues. These isoforms were Bax α, d, δ, and ζ. Exon 4 had a normal pattern in all cases of breast cancer. There was a statistically significant difference in the frequency distribution of the G(-248)A genotypes in the breast cancer tissues with grade 3+high, T2 stage, lobular +other, and PR −ve subgroups. In this study, Bak expression seems to lead to development of breast cancer and affects the disease progression. Also, Bax d and Bax δ could be used as risk factor and biomarker for breast cancer with the distribution of G284A.

Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance

“…Furthermore, mutations of Bax exons lead to chemoresistance. Bax gene mutation is highly involved in various types of human cancer . Moshynska et al reported the effect of promoter SNP in the human Bax gene expression .…”

BAX and SMAC Regulate Bistable Properties of the Apoptotic Caspase System

“…The results so far indicate that the model that we have generated reflects the behaviour of the intrinsic apoptotic pathway and therefore can be used to analyse the relative contributions of BAX and SMAC to the irreversible activation of the system. Importantly, these proteins have been shown to be deregulated in several diseases such as cancer and neurodegeneration, where incorrect activation of apoptosis are hallmarks 4,6,26,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] . In the case of tumour cells, it has been shown that there is an increase of the threshold of apoptosis activation by downregulation of BAX and SMAC 16,31,35 .…”

“…Models developed including BAX and SMAC have shown that these proteins are key in the regulation of apoptotic commitment. BAX is the gateway to mitochondrial activation of intrinsic apoptosis and has been shown to form pores in the mitochondrial membrane resulting in the release of pro-apoptotic proteins [26][27][28] . SMAC is one of the proteins released from the mitochondria upon activation of the intrinsic apoptotic pathway and is and inhibitor of IAPs 13 .…”

“…Correct function of both BAX and SMAC is central to the regulation of apoptosis. Importantly, deregulation of these pro-apoptotic proteins has been described in tumours and patients with neurodegenerative diseases 4,6,26,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] .…”

Relación entre Polimorfismos de Nucleótido Simple (SNPs) en genes implicados en la proliferación celular, adhesión y mecanismos de supervivencia y la susceptibilidad al desarrollo del cáncer de mama

“…Por otra parte, varios estudios han informado que el polimorfismo G(-248)A en el promotor de Bax (Figura 19), podría ser utilizado como un biomarcador de susceptibilidad o protección al cáncer, mientras que otros no han encontrado asociación alguna (Sahu y Choudhuri, 2013;Saxena et al, 2002;Skogsberg et al, 2006). En pacientes con leucemia linfocítica crónica se ha encontrado que este SNP se asocia con la reducción en la expresión proteica, estadio avanzado de la enfermedad y una respuesta incompleta al tratamiento (Kholoussi et al, 2014).…”