title: Expression of the stress response oncoprotein LEDGF/p75 in human cancer: a study of 21 tumor types.
abstract: Oxidative stress-modulated signaling pathways have been implicated in carcinogenesis and therapy resistance. The lens epithelium derived growth factor p75 (LEDGF/p75) is a transcription co-activator that promotes resistance to stress-induced cell death. This protein has been implicated in inflammatory and autoimmune conditions, HIV-AIDS, and cancer. Although LEDGF/p75 is emerging as a stress survival oncoprotein, there is scarce information on its expression in human tumors. The present study was performed to evaluate its expression in a comprehensive panel of human cancers. Transcript expression was examined in the Oncomine cancer gene microarray database and in a TissueScan Cancer Survey Panel quantitative polymerase chain reaction (Q-PCR) array. Protein expression was assessed by immunohistochemistry (IHC) in cancer tissue microarrays (TMAs) containing 1735 tissues representing single or replicate cores from 1220 individual cases (985 tumor and 235 normal tissues). A total of 21 major cancer types were analyzed. Analysis of LEDGF/p75 transcript expression in Oncomine datasets revealed significant upregulation (tumor vs. normal) in 15 out of 17 tumor types. The TissueScan Cancer Q-PCR array revealed significantly elevated LEDGF/p75 transcript expression in prostate, colon, thyroid, and breast cancers. IHC analysis of TMAs revealed significant increased levels of LEDGF/p75 protein in prostate, colon, thyroid, liver and uterine tumors, relative to corresponding normal tissues. Elevated transcript or protein expression of LEDGF/p75 was observed in several tumor types. These results further establish LEDGF/p75 as a cancer-related protein, and provide a rationale for ongoing studies aimed at understanding the clinical significance of its expression in specific human cancers.
authors.affiliation: Center for Health Disparities and Molecular Medicine and Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, United States of America. abasu@llu.edu
authors.forename: Anamika
authors.initials: A
authors.lastname: Basu
authors.forename: Heather
authors.initials: H
authors.lastname: Rojas
authors.forename: Hiya
authors.initials: H
authors.lastname: Banerjee
authors.forename: Irena B
authors.initials: IB
authors.lastname: Cabrera
authors.forename: Kayla Y
authors.initials: KY
authors.lastname: Perez
authors.forename: Marino
authors.initials: M
authors.lastname: De León
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Casiano
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D051381:Rats
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor