title: PDRG1, a novel tumor marker for multiple malignancies that is selectively regulated by genotoxic stress.
abstract: We have previously cloned and characterized a novel p53 and DNA damage-regulated gene named PDRG1. PDRG1 was found to be differentially regulated by ultraviolet (UV) radiation and p53. In this study, we further investigated stress regulation of PDRG1 and found it to be selectively regulated by agents that induce genotoxic stress (DNA damage). Using cancer profiling arrays, we also investigated PDRG1 expression in matching normal and tumor samples representing various malignancies and found its expression to be upregulated in multiple malignancies including cancers of the colon, rectum, ovary, lung, stomach, breast and uterus when compared to their respective matched normal tissues. Western blot and immunohistochemical analyses were also performed on select specimen sets of colon cancers and matching normal tissues and the results also indicated PDRG1 overexpression in tumors relative to normal tissues. To gain insight into the function of PDRG1, we performed PDRG1 knockdown in human colon cancer cells and found its depletion to result in marked slowdown of tumor cell growth. These results suggest that PDGR1 may be linked to cell growth regulation. Yeast two-hybrid screen also led to the identification of PDCD7, CIZ1 and MAP1S as PDRG1-interacting proteins that are involved in apoptosis and cell cycle regulation which further implicate PDRG1 in controlling cell growth regulation. Taken together, our results indicate that PDRG1 expression is increased in multiple human malignancies suggesting it to be a high-value novel tumor marker that could play a role in cancer development and/or progression.
authors.affiliation: Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY, USA.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Jiang
authors.forename: Xiuquan
authors.initials: X
authors.lastname: Luo
authors.forename: Jingxue
authors.initials: J
authors.lastname: Shi
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: M Saeed
authors.initials: MS
authors.lastname: Sheikh
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C400423:Ciz1 protein, human; D004268:DNA-Binding Proteins; C493240:MAP1S protein, human; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C485562:PDCD7 protein, human; C478985:PDRG1 protein, human; D014157:Transcription Factors