Saving Tabby; C35 Expression as a Cancer Marker?; Interdisciplinary Research

Front Page Saving Tabby; C35 Expression as a Cancer Marker?; Interdisciplinary Research Saving Tabby Reprinted with permission from Nature © online April 7, 2003 Researchers in Switzerland reversed a genetic developmental defect in mice by injecting their pregnant mothers with a recombinant protein. These smaller-than-normal patients, so-called Tabby mice, lack specialized hairs, teeth, and sweat glands. Both Tabby and its human counterpart of this disease, an X-linked form of ectodermal dysplasia, result from a mutated gene that is highly conserved in mouse and man, ectodysplasin A, or EDA. Pascal Schneider and colleagues at the University of Lausanne created a friendly Trojan horse of sorts by fusing a correct version of the EDA receptor-binding domain to the C-terminus of immunoglobulin G1's Fc domain. The Fc fusion ensures delivery through placental protein receptors as mother mouse passes immune protection on to her developing pups. The EDA enters the fetal systems to aid development. The treatment resulted in larger mice that had more specialized hair types, better tooth development, and sweat glands (O. Gaide et al., "Permanent correction of an inherited ectodermal dysplasia with recombinant EDA," Nat Med, doi:10.1038/nm861, April 7, 2003). The EDA ligand is expressed in the skin of normal adult mice, but the effects persisted for treated Tabbys. Says Schneider: "It must have a function, otherwise it would not be expressed ... but we can tell from this experiment that EDA has proven not necessary to maintain the structure which has been created." --Brendan A. Maher Interdisciplinary Research These papers were selected from multiple disciplines from the Faculty of 1000, a web-based literary awareness tool (www.facultyof1000.com) S. Shi et al., "Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity," Cell, 112:63-75, Jan. 10, 2003. "This paper reveals the importance of the PI 3-kinase signaling pathway and the specific localization of mPar3/mPar6 in the selection of the axonal process over dendritic processes of a neuron during development." --Silvia Arber, University of Basel S. Park et al., "Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms," Science, 299:1061-4, Feb. 14, 2003. "This elegant study demonstrates that a primary mechanism by which scaffolding proteins regulate signal transmission through the mitogen-activated protein (MAP) kinase is through the colocalization of the signaling components." --Deborah Morrison, National Cancer Institute V. Starai et al., "Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine," Science, 298:2390-2, Dec. 20, 2002. "The authors show that acetyl-coenzyme A synthetase (Acs), a key metabolic enzyme, is regulated by acetylation and that the NAD-dependent deacetylation activity of CobB2 is required to activate Acs." --Robert Dutnall, University of California, San Diego J. Culi et al., "Boca, an endoplasmic reticulum protein required for wingless signaling and trafficking of LDL receptor family members in Drosophila," Cell, 112:343-54, Feb. 7, 2003. "This paper provides another example of the surprising fact that certain chaperones specifically assist the folding of distinct subsets of secreted proteins." --Andrew Lumsden, King's College London C35 Expression as a Cancer Marker? Courtesy of National Cancer Institute A novel gene, C35, appears to be a good prognostic factor for breast cancer and could lead to vaccine and antibody treatments, say investigators at the University of Rochester School of Medicine and Dent-istry. Research showed that C35 appeared in more than 60% of tumorigenic cell lines and tumor samples, according to Deepak Sahasrabudhe. He recently discussed the results via conference call; he had been slated to discuss them in early April at the American Association for Cancer Research 2003 meeting, which was postponed due to the severe acute respiratory syndrome (SARS) outbreak in Toronto. The only other tissue type in which C35 appeared is testis. The gene lies on chromosome 17, adjacent to C-erbB2, which encodes HER2/neu (human epidermal growth factor receptor2), a major therapeutic target. HER2/neu is co-expressed in some C35-positive tumors, but not observed in C35-negative tumors. Though C35 has no known function, Sahasrabudhe says that the 115-amino-acid protein contains some phosphorylation sites and a prenylation site that may anchor it to the cell membrane. Results have not yet been published. Sahasrabudhe says that a Rochester-based company that he cofounded, Vaccinex, will investigate the feasibility of creating a vaccine therapy or an antibody therapy, even though C35 is believed to be mainly cytoplasmic. "It's counterintuitive to think something that is intracellular would be amenable to an antibody-based therapy, but when tumors undergo apoptosis or necrosis in histologic sections, we have observed C35 in the interstitial spaces," he says. --Brendan A. Maher function sendData() { document.frm.pathName.value = location.pathname; result = false if (document.frm.score[0].checked) result = true; if (document.frm.score[1].checked) result = true; if (document.frm.score[2].checked) result = true; if (document.frm.score[3].checked) result = true; if (document.frm.score[4].checked) result = true; if (!result) alert("Please select") return result; } .myradio{background-color : #94bee5} Please indicate on a 1 - 5 scale how strongly you would recommend this article to your colleagues? Not recommended 1 2 3 4 5 Highly recommended Please register your vote

Saving Tabby; C35 Expression as a Cancer Marker?; Interdisciplinary Research

Front Page

Saving Tabby; C₃₅ Expression as a Cancer Marker?; Interdisciplinary Research

Interested in reading more?

Become a Member of