Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: A systematic expression analysis

<p>Abstract</p> <p>Background</p> <p>The inter-alpha-trypsin inhibitors (ITI) are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded by <it>AMBP </it>– and five homologous heavy chains (encoded by <it>ITIH1</it>, <it>ITIH2</it>, <it>ITIH3</it>, <it>ITIH4</it>, and <it>ITIH5</it>), contributing to extracellular matrix stability by covalent linkage to hyaluronan. So far, ITIH molecules have been shown to play a particularly important role in inflammation and carcinogenesis.</p> <p>Methods</p> <p>We systematically investigated differential gene expression of the <it>ITIH </it>gene family, as well as <it>AMBP </it>and the interacting partner <it>TNFAIP6 </it>in 13 different human tumor entities (of breast, endometrium, ovary, cervix, stomach, small intestine, colon, rectum, lung, thyroid, prostate, kidney, and pancreas) using cDNA dot blot analysis (Cancer Profiling Array, CPA), semiquantitative RT-PCR and immunohistochemistry.</p> <p>Results</p> <p>We found that <it>ITIH </it>genes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus, <it>ITIH </it>genes may represent a family of putative tumor suppressor genes that should be analyzed in greater detail in the future. For an initial detailed analysis we chose <it>ITIH2 </it>expression in human breast cancer. Loss of <it>ITIH2 </it>expression in 70% of cases (n = 50, CPA) could be confirmed by real-time PCR in an additional set of breast cancers (n = 36). Next we studied ITIH2 expression on the protein level by analyzing a comprehensive tissue micro array including 185 invasive breast cancer specimens. We found a strong correlation (p < 0.001) between ITIH2 expression and estrogen receptor (ER) expression indicating that ER may be involved in the regulation of this ECM molecule.</p> <p>Conclusion</p> <p>Altogether, this is the first systematic analysis on the differential expression of <it>ITIH </it>genes in human cancer, showing frequent downregulation that may be associated with initiation and/or progression of these malignancies.</p

Tellurides from Sunrise Dam gold deposit, Yilgarn Craton, Western Australia: A new occurrence of nagyagite

© Springer The original publication can be found at www.springerlink.comThe complex Pb-Sb-Au tellurosulfide nagyágite is found together with eight tellurides (hessite, petzite, calaverite, altaite, tellurantimony (and Bi-bearing tellurantimony), melonite, tetradymite and an unnamed Au(Ag)-As-telluride) in sulfide-sulfosalt assemblages from late, high-grade veins (D4) and post-D4 veinlets in the world-class orogenic gold deposit at Sunrise Dam, Eastern Goldfields Province of the Archaean Yilgarn Craton, Western Australia. The composition of nagyágite at Sunrise Dam conforms to ideal stoichiometry, with negligible As content and Au/(Au+Te) ratio of 0.325 [i.e., (Pb4.84Sb1.10 As0.05)5.99S5.99(Au0.98 Te2.03)3.01]. The diverse mineralogy of the post-D4 veinlets, relative to the host veins, is attributed to small-scale reaction fronts established along zones of replacement at the polished section scale. The association of telluride assemblages and native gold is interpreted in terms of remobilization of ore components (including Ag, Sb, Te and Au) from the pre-existing assemblages, and their redeposition during subsequent tectonic events. The presence of nagyágite and Au-Ag tellurides in veins, in quantities that may be significant in economic terms, as well as the character of their breakdown products, have implications for ore processing and gold recovery, as well as for the genetic interpretation of the deposit. The strong structural control upon formation of the telluride-bearing assemblages at Sunrise Dam and the ability of these minerals to reflect changes in the local environment, contradicts the current view that these tellurides have a magmatic affiliation.Y.-H. Sung, C. L. Ciobanu, A. Pring, J. Brügger, W. Skinner, N. J. Cook and M. Nugu