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: Anamika Basu, Heather Rojas, Hiya Banerjee, Irena B Cabrera, Kayla Y Perez, Marino De León, Carlos A Casiano
• Journal: PloS one (PLoS One) Vol. 7 Issue 1 Pg. e30132 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22276150 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Intercellular Signaling Peptides and Proteins
• lens epithelium-derived growth factor

Topics

• Animals
• Cell Line, Tumor
• Female
• Humans
• Immunohistochemistry
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• Male
• Neoplasms (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Polymerase Chain Reaction
• RNA Interference
• Rats