Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain ITIH genes in multiple human solid tumors: A systematic expression analysisReportar como inadecuado




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BMC Cancer

, 8:25

First Online: 28 January 2008Received: 30 July 2007Accepted: 28 January 2008DOI: 10.1186-1471-2407-8-25

Cite this article as: Hamm, A., Veeck, J., Bektas, N. et al. BMC Cancer 2008 8: 25. doi:10.1186-1471-2407-8-25

Abstract

BackgroundThe inter-alpha-trypsin inhibitors ITI are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded by AMBP – and five homologous heavy chains encoded by ITIH1, ITIH2, ITIH3, ITIH4, and ITIH5, 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.

MethodsWe systematically investigated differential gene expression of the ITIH gene family, as well as AMBP and the interacting partner TNFAIP6 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.

ResultsWe found that ITIH genes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus, ITIH 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 ITIH2 expression in human breast cancer. Loss of ITIH2 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.

ConclusionAltogether, this is the first systematic analysis on the differential expression of ITIH genes in human cancer, showing frequent downregulation that may be associated with initiation and-or progression of these malignancies.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-8-25 contains supplementary material, which is available to authorized users.

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