Methansarcina mazei Gö1 DNA arrays were constructed and used to evaluate the genomic expression patterns of cells grown on either of two alternative methanogenic substrates, acetate or methanol, as sole carbon and energy source. Analysis of differential transcription across the genome revealed two functionally grouped sets of genes that parallel the central biochemical pathways in, and reflect many known features of, acetate and methanol metabolism. These include the acetate-induced genes encoding acetate activating enzymes, acetyl-CoA synthase/CO dehydrogenase, and carbonic anhydrase. Interestingly, additional genes expressed at significantly higher levels during growth on acetate included two energy-conserving complexes (the Ech hydrogenase, and the A1A0-type ATP synthase). Many previously unknown features included the induction by acetate of genes coding for ferredoxins and flavoproteins, an aldehyde:ferredoxin oxidoreductase, enzymes for the synthesis of aromatic amino acids, and components of iron, cobalt and oligopeptide uptake systems. In contrast, methanol-grown cells exhibited elevated expression of genes assigned to the methylotrophic pathway of methanogenesis. Expression of genes for components of the translation apparatus was also elevated in cells grown in the methanol medium relative to acetate, and was correlated with the faster growth rate observed on the former substrate. These experiments provide the first comprehensive insight into substrate-dependent gene expression in a methanogenic archaeon. This genome-wide approach, coupled with the complementary molecular and biochemical tools, should greatly accelerate the exploration of Methanosarcina cell physiology, given the present modest level of our knowledge of these large archaeal genomes.

The transforming growth factor beta 1 (TGF-beta1) is a multifunctional cytokine with several regulatory activities in tumor cells affecting growth, differentiation, and function. Alterations in gene expression, secretion, and regulation of TGF-beta1 may lead to a favorable environment for tumor development by angiogenesis stimulation and immune system suppression. We evaluated the influence of the TGFB1 polymorphisms by ARMS-PCR, Leu10Pro, and Arg25Pro, on prostate cancer (PCa) and benign prostatic hyperplasia (BPH). We assessed TGFB1 polymorphisms and their relation to mRNA levels (semi-quantitative RT-PCR) in blood samples as well as the implications in disease occurrence and progression. Peripheral blood samples from 175 patients were analyzed as to 92 BPH and 83 PCa. Samples obtained from 132 healthy males were used as negative controls. PCa patients with a Gleason score greater than 7 presented a higher frequency of the C allele (Leu10Pro). This allele was associated with a higher risk of developing PCa and BPH compared to the population (2.6 and 3.6 times higher, respectively). Patients with TGFB1 transcript levels equal to or more than 70% higher than control levels presented a 5.34 and 2.14-fold higher risk of having PCa and BPH, respectively, relative to the population. No association was detected between polymorphisms and mRNA levels. The C allele of the Leu10Pro polymorphism may predispose men to a more rapid cancer progression. Additionally, higher mRNA levels in the peripheral blood of PCa patients suggest that tumor cells may be disseminated in the circulation and could be used as a biomarker for extra-capsular invasion.