Möllerström et al. BMC Cancer 2010, 10:296 http://www.biomedcentral.com/1471-2407/10/296 Page 6 of 11 Figure 2 Various sub-cellular location of the BTG2 protein in even within one sample. One TMA sample showing cytoplasm and cell membrane expression of BTG2 in a part of the sample and exclusively membranous expression in another part of the sample. Brown colour indicates BTG2 staining. observed cytoplasm and cell membrane expression, but no nuclear expression. The various sub-cellular locations of BTG2 could indicate that the protein is expressed in different cellular compartments during altering condi- tions, such as cell cycle phase, differentially expressed in diverse tissue types, or due to varying specificity of differ- ent antibodies. The BTG2 gene is located at the 1q32 chromosomal region, which was gained in a significantly higher propor- tion of 10-year survivors than in deceased lymph node- negative breast cancer patients in a previous study [10]. The gene belongs to the structurally homogeneous BTG family of which five genes have been identified in human, BTG1, BTG2, BTG3, Tob and Tob2. The BTG2 protein is highly conserved and shares 94% homology with the murine equivalent [20]. BTG2 is a tumour suppressor gene [21-23] which is directly regulated by p53 and involved in p53-mediated response to DNA damage [24]. According to the literature, BTG2 is involved in cell cycle arrest in the transition from G1 to S phase [25,26]. In addition, BTG2 can regulate G2 to M cell cycle arrest independent of p53 [27,28]. BTG2 is known to mediate chemotherapy induced apoptosis in cancer cells [29-31] and a study by Lim et al. indicates that BTG2 enhances cancer cell death by accumulation of H2O2 [32]. Down-regulation of BTG2 has been observed in several cancer types such as prostate cancer, breast cancer and gliomas [17,18,33]. In this study 78% of the breast cancer samples showed moderate to high expression of BTG2 in the majority of tumour cells. Nevertheless, BTG2 was sig- nificantly down-regulated in tumours from dead patients compared to tumours from alive patients, both in overall expression and cell membrane specific expression. This finding suggests that high total BTG2 or specific cell membrane expression may contribute to a prolonged sur- vival. A previous study analysed BTG2 protein expression and correlated decreased nucleus expression to a more aggressive phenotype of breast cancer, although they did not detect a significant difference in survival [34]. This discrepancy could be due to the use of different BTG2 Figure 3 Kaplan-Meier survival curves illustrating the effect of BTG2 expression. The Kaplan-Meier curves show the difference in survival be- tween patients with tumours that revealed any BTG2 expression and patients whose tumours did not (A), as well as the difference in survival between patients with tumours that revealed cell membrane specific BTG2 expression and patients whose tumours did not (B). Solid lines represent patients whose tumours expressed BTG2 and dashed lines represent patients whose tumours did not. The p-values for the difference between the curves were calculated using a generalized Wilcoxon test.