Retroviral activation of the mir-106a microRNA cistron in T lymphoma

Retroviral insertion into a host genome is a powerful tool not only for the discovery of cancer genes, but also for the discovery of potential oncogenic noncoding RNAs. In a large-scale mouse T lymphocyte tumor screen we found a high density of integrations upstream of the mir-106a microRNA cistron. In tumors containing an integration, the primary transcript encoding the mir-106a cistron was overexpressed five to 20-fold compared with that of control tumors; concomitantly, the mature mir-106a and mir-363 microRNAs were highly overexpressed as well. These findings suggest the mir-106a cistron plays an important role in T cell tumorigenesis

Orphan receptor GPR110, an oncogene overexpressed in lung and prostate cancer

<p>Abstract</p> <p>Background</p> <p>GPR110 is an orphan G protein-coupled receptor--a receptor without a known ligand, a known signaling pathway, or a known function. Despite the lack of information, one can assume that orphan receptors have important biological roles. In a retroviral insertion mutagenesis screen in the mouse, we identified GPR110 as an oncogene. This prompted us to study the potential isoforms that can be gleaned from known GPR110 transcripts, and the expression of these isoforms in normal and transformed human tissues.</p> <p>Methods</p> <p>Various epitope-tagged isoforms of GPR110 were expressed in cell lines and assayed by western blotting to determine cleavage, surface localization, and secretion patterns. GPR110 transcript and protein levels were measured in lung and prostate cancer cell lines and clinical samples, respectively, by quantitative PCR and immunohistochemistry.</p> <p>Results</p> <p>We found four potential splice variants of GPR110. Of these variants, we confirmed three as being expressed as proteins on the cell surface. Isoform 1 is the canonical form, with a molecular mass of about 100 kD. Isoforms 2 and 3 are truncated products of isoform 1, and are 25 and 23 kD, respectively. These truncated isoforms lack the seven-span transmembrane domain characteristic of GPR proteins and thus are not likely to be membrane anchored; indeed, isoform 2 can be secreted. Compared with the median gene expression of ~200 selected genes, GPR110 expression was low in most tissues. However, it had higher than average gene expression in normal kidney tissue and in prostate tissues originating from older donors. Although identified as an oncogene in murine T lymphomas, GPR110 is greatly overexpressed in human lung and prostate cancers. As detected by immunohistochemistry, GPR110 was overexpressed in 20 of 27 (74%) lung adenocarcinoma tissue cores and in 17 of 29 (59%) prostate adenocarcinoma tissue cores. Additionally, staining with a GPR110 antibody enabled us to differentiate between benign prostate hyperplasia and potential incipient malignancy.</p> <p>Conclusion</p> <p>Our work suggests a role for GPR110 in tumor physiology and supports it as a potential therapeutic candidate and disease marker for both lung and prostate cancer.</p

Retroviral activation of the mir-106a microRNA cistron in T lymphoma

Abstract Retroviral insertion into a host genome is a powerful tool not only for the discovery of cancer genes, but also for the discovery of potential oncogenic noncoding RNAs. In a large-scale mouse T lymphocyte tumor screen we found a high density of integrations upstream of the mir-106a microRNA cistron. In tumors containing an integration, the primary transcript encoding the mir-106a cistron was overexpressed five to 20-fold compared with that of control tumors; concomitantly, the mature mir-106a and mir-363 microRNAs were highly overexpressed as well. These findings suggest the mir-106a cistron plays an important role in T cell tumorigenesis.</p

Application of HB17, an Arabidopsis class II homeodomain-leucine zipper transcription factor, to regulate chloroplast number and photosynthetic capacity

Transcription factors are proposed as suitable targets for the control of traits such as yield or food quality in plants. This study reports the results of a functional genomics research effort that identified ATHB17, a transcription factor from the homeodomain-leucine zipper class II family, as a novel target for the enhancement of photosynthetic capacity. It was shown that ATHB17 is expressed natively in the root quiescent centre (QC) from Arabidopsis embryos and seedlings. Analysis of the functional composition of genes differentially expressed in the QC from a knockout mutant (athb17-1) compared with its wild-type sibling revealed the over-representation of genes involved in auxin stimulus, embryo development, axis polarity specification, and plastid-related processes. While no other phenotypes were observed in athb17-1 plants, overexpression of ATHB17 produced a number of phenotypes in Arabidopsis including enhanced chlorophyll content. Image analysis of isolated mesophyll cells of 35S::ATHB17 lines revealed an increase in the number of chloroplasts per unit cell size, which is probably due to an increase in the number of proplastids per meristematic cell. Leaf physiological measurements provided evidence of improved photosynthetic capacity in 35S::ATHB17 lines on a per unit leaf area basis. Estimates of the capacity for ribulose-1,5-bisphosphate-saturated and -limited photosynthesis were significantly higher in 35S::ATHB17 lines