PLAGL1 protein is differentially expressed in the nephron segments and collecting ducts in human kidney

Abstract

Introduction. PLAGL1 (pleiomorphic adenoma gene-like 1) is a C2H2-type zinc finger transcription factor associated with the regulation of cell growth and development. Although PLAGL1 expression in kidney was assessed by biochemical methods, the exact localization of the PLAGL1 protein in human kidney has not yet been described. Material and methods. Macroscopically unchanged specimens of kidney tissue were collected from 39 patients undergoing nephrectomy due to renal cell carcinoma. H & E staining of paraffin sections was used to assess histology of the kidney whereas immunohistochemistry was used to localize PLAGL1 protein in kidney compartments. In addition, database sequences search for putative PLAGL1 binding sites among the kidney-related genes was performed. Results. PLAGL1 staining intensity differed depending on the kidney compartment. Strong PLAGL1 immunoreactivity was found in thick ascending limbs of Henle's loop, distal tubules and collecting ducts, whereas PLAGL1 expression in proximal tubules and renal corpuscles (including podocytes) was moderate and weak, respectively. By the in sillico screening of promoter sequences for PLAGL1 specific DNA-binding sites GGG-GCCCC we designated 43 candidate genes for PLAGL1-regulated genes. Analysis of their functional annotations identified three significantly over-represented gene sets: inositol phosphate metabolic processes (GO), endocrine and other factor-regulated calcium reabsorption (KEGG) and calcium signaling pathways (KEGG). Conclusion. Differences in the renal expression of PLAGL1 suggest that this protein may be involved in the regulation of several cellular pathways both as transcriptional factor and coactivator/corepressor of other transcription factors reflecting its role in the cell type-specific control

Colorectal cancer patients exhibit increased levels of galanin in serum and colon tissues

“…IHC, defined as positive immunoreactivity for GAL, was performed as described previously by Godlewski et al (19) with certain modifications. The sections were subjected to antigen retrieval by microwaving for 20 min in retrieval solution buffer (pH 6.0; Leica, Wetzlar, Germany) and incubated with 3% H 2 O 2 in methanol for 10 min followed by 2.5% normal horse serum (Vector Laboratories, Inc., Burlingame, CA, USA) in PBS for 30 min.…”

PLAGL1 gene function during hepatoma cells proliferation

“…In fact, punctual mutations of the PLAGL1 gene were detected in only 71 (0.3%) out of 21,029 tumor samples of all kind registered in the Catalog of Somatic Mutations in Cancer (COSMIC; http://cancer.sanger.ac.uk/cosmic ). To add more complexity, it has been also reported that overexpression of PLAGL1 was detected in some human neoplasms such as glioma and clear cell renal cell carcinoma, suggesting an oncogenic function, as well [ 28 , 29 ]. As regard to HCC, Midorikawa et al found that LOH at the chromosome region 6q24, hypermethylation of PLAGL1 promoter at the remaining allele and low mRNA levels were frequent in tissue samples from patients with hepatoma [ 26 ].…”

“…Since it was first described, the gene has been considered a tumor suppressor gene (TSG) [ 27 ], and all this evidence provided support for such classification. However, overexpression of PLAGL1 was detected in some human neoplasms such as glioma and clear cell renal cell carcinoma suggesting an oncogenic function, as well [ 28 , 29 ].…”

The Immunoexpression of YAP1 and LATS1 Proteins in Clear Cell Renal Cell Carcinoma: Impact on Patients’ Survival

“…Immunohistochemical (IHC) analysis was performed as described previously by Godlewski et al [ 20 ] with some modification. The sections were subjected to an antigen retrieval procedure by microwaving in Retrieval Solution Buffer (pH 6.0; Leica, Wetzlar, Germany), incubated with 3% H 2 O 2 in methanol for 30 min, and then in commercial normal horse serum (Vector Laboratories, Inc., Burlingame, CA, USA) for 30 min.…”