Abstract
Abstract INTRODUCTION: Guanine nucleotide binding protein beta polypeptide 1 (GNB1) integrates signals between receptors and effector proteins and regulates certain signal transduction receptors and effectors. We have hypothesised that GNB1 is involved in the anti-apoptosis pathway mediated by mTor. Therefore, this protein may play role in human carcinogenesis, however, there has been no investigations of this potential role published in the literature. The aim of the study was to investigate the mRNA expression of GNB1 in human breast cancer and examine the relationship between its expression and the tumour characteristics and disease outcome. Furthermore, the correlation between GNB1 and mTORC1 was also investigated. METHODS: Specimens of breast cancer (BC) tissues (N = 136) and normal tissues (N = 30) underwent RNA extraction and reverse transcription. GNB1 transcript levels were determined using real-time quantitative PCR. Expression levels were analysed against clinicopathological data accrued over a 10 year follow-up period. RESULTS: Significantly higher mRNA transcript levels were found in the breast cancer specimens compared to normal glandular tissue in paired samples (p = 0.0029). The expression of GNB1 mRNA was demonstrated to increase with increasing TNM stage (from 0.01 to 15.9) and this reached statistical significance when comparing TNM1 vs. TNM2/3/4 (p = 0.036). Furthermore, the expression levels increased with increasing tumour grade and this reached statistical significance when comparing grade 2 vs. grade 3 (p = 0.006). GNB1 expression was found to be higher in ductal tumours compared with non-ductal tumours (p = 0.0081). The patients who developed recurrent disease or died from breast cancer had higher expression levels than those who had been disease-free after a median follow-up period of 10 years (p = 0.017). Those who died from breast cancer had significantly higher levels than those who have remained disease-free (33.9 vs. 0.01, p = 0.0009). GNB1 showed a significantly positive correlation with mTORC1 mRNA levels (r = 0.57, p < 0.000001). CONCLUSION: GNB1 expression was found to be significantly higher in BC specimens compared to normal breast tissue. Higher transcript levels were significantly associated with unfavourable pathological parameters and adverse clinical outcomes. These observations in addition to the positive correlation with mTORC1 levels support the hypothesis that GNB1 is an important upstream component of the anti-apoptosis pathway and, therefore, can be a potential target for therapeutic intervention in human breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-04-08.
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