Quantitative expression analysis of the apoptotic gene BCL2L12 in breast cancer: association with clinical and molecular prognostic parameters

Apoptosis is a highly orchestrated, genetically regulated form of cell death, the impairment of which is crucial in breast cancer (BC) development and progression. BCL2L12, a member of the BCL2 family of apoptosis-related genes, has been studied in various malignancies, revealing its potential role as a tumor biomarker. It has been recently found that BCL2L12 is subjected to alternative splicing, resulting in the generation of 13 alternatively spliced variants. The aim of this study was the quantification of BCL2L12 splice variants 1 and 2 (v.1 and v.2) expression at the mRNA level and the assessment of their biomarker potential in BC

The loss of the tumour-suppressor miR-145 results in the shorter disease-free survival of prostate cancer patients

Background: Prostate cancer (PCa) is characterised by great heterogeneity of the disease progression rate. Tumours range from insignificant and not life threatening to high risk for relapse ones. Consequently, a large number of patients undergo unnecessary treatment. miR-145 is a well-documented tumour suppressor and its expression, which is regulated by the p53 pathway, has been found to be decreased in the majority of human malignancies. The aim of our study was to evaluate the clinical utility of miR-145 for the prognostication of PCa. Methods: Total RNA was isolated from 137 prostate tissue specimens obtained from 73 radical prostatectomy-treated PCa patients and 64 transurethral- or open prostatectomy-treated benign prostate hyperplasia (BPH) patients. Following polyadenylation and reverse transcription, miR-145 levels were determined by quantitative real-time PCR assay, using SNORD48 (RNU48) for normalisation purposes. Results: Downregulated miR-145 expression was found in PCa compared with BPH patients. The reduction of miR-145 expression in PCa was correlated with higher Gleason score, advanced clinical stage, larger tumour diameter and higher prostate-specific antigen (PSA) and follow-up PSA levels. In addition, higher risk for biochemical recurrence and significantly shorter disease-free survival (DFS) was found for the PCa patients expressing lower miR-145. Focusing on ‘low- and intermediate-recurrence risk’ PCa patients, miR-145 loss was revealed to be a reliable predictor of biochemical relapse and poor DFS independent from Gleason score, clinical stage, PSA and patients’ age. Conclusion: The loss of the tumour-suppressor miR-145 increases the risk for disease progression and predicts the poor survival of PCa patients

Codon 89 polymorphism in the human 5 α -reductase gene in primary breast cancer

The enzyme human steroid 5-α reductase type II (SRD5A2) and androgen receptor (AR) are critical mediators of androgen action, suggesting a potential role in hormonally related cancers. The SRD5A2 gene harbours two frequent polymorphic sites, one in the coding region, at codon 89 of exon 1, where valine is substituted by leucine (V89L) and the other in the 3′ untranslated region (3′ UTR) where a variable number of dinucleotide TA repeat lengths exists. The V89L polymorphism is known to alter the activity of this enzyme. In the present study we examined 144 sporadic breast tumours from Italian patients for the V89L and TA polymorphisms by sequence and fragment analysis, respectively. Tumour extract prostate specific antigen (PSA) concentration as well as a number of well-established clinical and pathological parameters were evaluated. The results show that 53% of the tumours were homozygous for VV alleles, 37% were heterozygous for VL alleles and 10% were homozygous for LL alleles. TA(0) repeats were found in tumours with VV, LL and VL genotypes. TA(9) repeats were only found in VV homozygotes and were totally absent from either LL homozygotes or VL heterozygotes. PSA expression was significantly elevated in tumours with VV genotype. The presence of LL alleles in breast tumours is associated with earlier onset and shorter disease-free (RR = 2.65;P = 0.013) and overall survival (RR = 3.06;P = 0.014) rates. The VV genotype is associated with a more favourable prognosis. Our study suggests that the polymorphism in codon 89 of exon 1 of the human 5α-reductase gene is related with TA repeat genotypes, PSA expression and breast cancer prognosis. More specifically, we found that the LL genotype is also associated with earlier onset and more aggressive forms of breast cancer. Long-term-outcome studies are needed to investigate the relevance of this polymorphism to breast cancer susceptibility. © 2001 Cancer Research Campaign http://www.bjcancer.co

BAX (BCL2-associated X protein)

Review on BAX (BCL2-associated X protein), with data on DNA, on the protein encoded, and where the gene is implicated

Overexpression of matrix-metalloproteinase-9 in human breast cancer: a potential favourable indicator in node-negativeatients

Matrix metalloprotease-9 (MMP-9; 92 kDa type IV collaganase, gelatinase B) is regarded as, important for degradation of the basement membrane and extracellular matrix during cancer invasion and other tissue-remodelling events. In this study we evaluate the prognostic value of MMP-9, by immunoperoxidase staining in a series of 210 breast cancer tissues. The results were quantitated using the HSCORE system, which consider both staining intensity and the percentage of cells stained at given intensities. MMP-9 status was compared with the concentration of cytosolic Cathepsin-D and with other established prognostic factors, in terms of disease free survival and overall survival. The median follow-up period was 62 months. MMP-9 staining was observed primarily in cancer cells, and to a lesser degree in surrounding stromal cells. MMP-9 expression was not detected in normal breast tissue. Levels of MMP-9 expression below the cut-off point were more frequently observed in larger (P = 0.014), invasive ductal histologic (P = 0.037), progesterone receptor (PR)-negative and PR-strong positive tumours (P< 0.001), as well as samples belonging to patients with stage III-IV disease (P = 0.009) and age 45–55 years (P = 0.011). In univariate analysis, node-negative breast cancer patients with tumors positive for MMP-9 had a considerable reduction in risk for relapse (RR = 0.45;P = 0.039) or death (RR = 0.32;P = 0.009). Multivariate analysis indicated that MMP-9 status was an independent favourable predictor of OS (RR = 0.47;P = 0.034) in node-negative but not in node-positive patients. Our results suggest that MMP-9 may be an independent favourable prognostic factor in node-negative breast cancer patients. The overexpression of MMP-9 in breast cancer may be also used as a marker to subdivide node negative breast cancer patients in order to determine the optimal treatment modality. © 2001 Cancer Research Campaign http://www.bjcancer.co

BCL2L12 (BCL2-like 12 (proline-rich))

Review on BCL2L12 (BCL2-like 12 (proline-rich)), with data on DNA, on the protein encoded, and where the gene is implicated

DDC (dopa decarboxylase (aromatic L-amino acid decarboxylase))

Review on DDC (dopa decarboxylase (aromatic L-amino acid decarboxylase)), with data on DNA, on the protein encoded, and where the gene is implicated