The promoter and the enhancer region of the KLK 3 (prostate specific antigen) gene is frequently mutated in breast tumours and in breast carcinoma cell lines

KLK3 or prostate specific antigen (PSA) is a serine protease, which is an established tumour marker of prostatic adenocarcinoma. PSA is now used widely for the diagnosis and monitoring of patients with prostate cancer. Recent studies have demonstrated that about 70% of breast cancers produce PSA. In this study, we examined the molecular mechanism underlying the expression of the PSA gene in breast cancer and breast cancer cell lines. We analysed nine breast tumours categorized on the basis of high- or low-PSA expression in tumour cytosols and four breast cancer cell lines. To determine abnormalities associated with PSA expression in breast tumours, genomic DNA was extracted and all five exons of the PSA gene were polymerase chain reaction (PCR) amplified and sequenced on both strands. PCR amplification was also performed for the promoter and enhancer elements of the PSA gene. No mutations were observed in the coding portion of the gene. A polymorphism was observed in exon 2 from three breast tumours. However, sequencing of the promoter and the enhancer elements of the PSA gene reveals several point mutations. Within a 5.8-kb promoter/enhancer region of the PSA gene, we detected 16 different mutational hotspots (appearing more than once in the nine tumours). Among these hotspots, two appeared in seven out of nine tumours. Most importantly, the androgen response element (ARE I) in the proximal promoter was found mutated in four tumours and in the breast carcinoma cell line MCF-7. Mutations associated with the ARE I have been shown previously to result in an 80% decrease in PSA gene expression. The mutations in the core enhancer and promoter region probably contribute to the aberrant expression of the PSA gene in breast tumours, possibly by altering the regulation of the gene by steroid hormones. © 1999 Cancer Research Campaig

Cavity ring-down spectroscopy measurements of the concentrations of C 2(X1Σg +) radicals in a DC arc jet reactor used for chemical vapour deposition of diamond films

Absorption spectroscopy measurements are reported of the absolute number density (3.0±0.9×1012 cm-3) and vibrational temperature (3000±500 K) of C2(X1Σ g+) radicals in a DC arc activated chemical vapour deposition reactor under the standard operating conditions (3.3% CH4 in H2 and 6.4 kW discharge) used to grow polycrystalline diamond films. The ratio of number densities of C2 radicals in their ground (X1Σg+) and low-lying electronically excited (a3Πu) states is close to that expected from a Boltzmann distribution at the measured temperature, despite the more rapid rates of reaction of C2(X) with H2 and hydrocarbon molecules. © 2003 Elsevier B.V. All rights reserved