Amplification of the BCAS2 gene at chromosome 1p13.3-21 in human primary breast cancer
ABSTRACT BCAS2 is a novel gene isolated from breast cancer cell line by differential display technique. Previously we reported that BCAS2 gene is localized on chromosome 1p13.3-21 and is up-regulated by gene amplification in breast cancer cell lines MCF-7 and BT-20. In this study, we investigated the amplification of the BCAS2 gene in a series of 104 gynecological primary tumors by means of Southern blot analysis. The BCAS2 gene was amplified in two of 60 primary breast cancer tissues, whereas no amplification was detected in any of endometrial (0/26) and cervical (0/18) tumor tissues. Gene amplification was also not detected in a series of pancreatic (0/9) and gastric (0/6) cancer cell lines. An enhanced green fluorescent protein assay revealed that BCAS2 protein seems to be translocated into the nucleus. Although frequent deletions of the proximal region of chromosome 1p13.3-21 have been found in primary breast cancer, our results support first evidence of amplification within this region and indicate that BCAS2 gene codes for a nuclear protein.
- SourceAvailable from: Xiao-feng Ding
[Show abstract] [Hide abstract]
- "In these cell lines, p53 activity is possibly prevented by other cellular factors. For example, BCAS2 gene is upregulated by gene amplification in breast cancer cell lines MCF-7  . BCAS2 protein directly interacts with p53 to reduce p53 transcriptional activity by mildly but consistently decreasing p53 protein . "
ABSTRACT: The putative CCDC106 protein was previously identified as a p53-interacting partner by automated yeast two-hybrid screening, but its sequence and function have not been validated experimentally. Here, we identified three variant transcripts of the CCDC106 gene; these transcripts differ in their second exons due to the use of different splice acceptor site, but encode an identical protein of 280 residues. A bipartite nuclear localisation signal at residues 151-164 mediates the nuclear localisation of CCDC106. Double immunofluorescence staining revealed the colocalisation of endogenous CCDC106 and p53 protein in nuclei. The in vivo interaction between CCDC106 and p53 was confirmed by a co-immunoprecipitation assay. Furthermore, we demonstrated that CCDC106 promotes the degradation of p53 protein and inhibits its transactivity.FEBS letters 02/2010; 584(6):1085-90. DOI:10.1016/j.febslet.2010.02.031 · 3.34 Impact Factor
[Show abstract] [Hide abstract]
- "However, since MCF-7 is a cancer cell line, there was a concern that high genome copy numbers in the cells may result in strong gene expression in the absence of HRG that may potentially obscure any HGR-related effects. Genes such as NCOA3, PPM1D, PSMD6 and BCAS2 were detected with high expression and copy numbers in MCF-7 cells (Figures 5 and 6), and these genes have been associated with breast cancer progression –. However, our analysis revealed that the overall correlation between average copy number and the extent of gene expression was surprisingly weak. "
ABSTRACT: Heregulin beta-1 (HRG) is an extracellular ligand that activates mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI3K)/Akt signaling pathways through ErbB receptors. MAPK and Akt have been shown to phosphorylate the estrogen receptor (ER) at Ser-118 and Ser-167, respectively, thereby mimicking the effects of estrogenic activity such as estrogen responsive element (ERE)-dependent transcription. In the current study, integrative analysis was performed using two tiling array platforms, comprising histone H3 lysine 9 (H3K9) acetylation and RNA mapping, together with array comparative genomic hybridization (CGH) analysis in an effort to identify HRG-regulated genes in ER-positive MCF-7 breast cancer cells. Through application of various threshold settings, 333 (326 up-regulated and 7 down-regulated) HRG-regulated genes were detected. Prediction of upstream transcription factors (TFs) and pathway analysis indicated that 21% of HRG-induced gene regulation may be controlled by the MAPK cascade, while only 0.6% of the gene expression is controlled by ERE. A comparison with previously reported estrogen (E2)-regulated gene expression data revealed that only 12 common genes were identified between the 333 HRG-regulated (3.6%) and 239 E2-regulated (5.0%) gene groups. However, with respect to enriched upstream TFs, 4 common TFs were identified in the 14 HRG-regulated (28.6%) and 13 E2-regulated (30.8%) gene groups. These results indicated that while E2 and HRG may induce common TFs, the regulatory mechanisms that govern HRG- and E2-induced gene expression differ.PLoS ONE 02/2008; 3(3):e1803. DOI:10.1371/journal.pone.0001803 · 3.23 Impact Factor
[Show abstract] [Hide abstract]
- "These genes passed the pre-processing filters in at least one out all of the samples studied. In addition, these genes were selected based on either 1. complete concordance (CCNB1) or discordance between either their measured expression levels (CASP5, CXCL10, MAPK4, RAB17, RME8 and TMPRSS5, and WNT10B) and/or being identified as a discriminating gene between the different platforms (ALG8, CASP5, CXCL10, MAPK4, RAG2, THEM2, TMPRSS5); 2. three genes (ERBB2, RPS6KB1, BCAS2) known to be highly expressed in MCF7 cells [29-32]. ERBB2 and RPS6KB1 corresponded to multiple targets to a different extent for the 3 platforms and were therefore excluded from the overall correlation calculation between RT-PCR and array data as well as from the all gene-wise comparison (see below). "
ABSTRACT: We compared the relative precision and accuracy of expression measurements obtained from three different state-of-the-art commercial short and long-oligonucleotide microarray platforms (Affymetrix GeneChip, GE Healthcare CodeLink and Agilent Technologies). The design of the comparison was chosen to judge each platform in the context of a multi-project program. All wet-lab experiments and raw data acquisitions were performed independently by each commercial platform. Intra-platform reproducibility was assessed using measurements from all available targets. Inter-platform comparisons of relative signal intensities were based on a common and non-redundant set of roughly 3,400 targets chosen for their unique correspondence toward a single transcript. Despite many examples of strong similarities we found several areas of discrepancy between the different platforms. We found a higher level of reproducibility from one-color based microarrays (Affymetrix and CodeLink) compared to the two-color arrays from Agilent. Overall, Affymetrix data had a slightly higher level of concordance with sample-matched real-time quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR) data particularly for detecting small changes in gene expression levels.BMC Genomics 02/2006; 7(1):51. DOI:10.1186/1471-2164-7-51 · 4.04 Impact Factor