title: Altered expression of the PLAGL1 (ZAC1/LOT1) gene in colorectal cancer: Correlations to the clinicopathological parameters.
abstract: Pleomorphic adenoma gene-like 1 gene (PLAGL1) encodes a zinc-finger nuclear transcription factor which promotes apoptosis and cell cycle arrest. Loss or downregulation of its expression has been observed in various human neoplasms. This study compared PLAGL1 expression in colorectal cancer (CRC) tissue and colon mucosa of healthy subjects at the mRNA and protein levels, and estimated its prognostic value. The PLAGL1 mRNA levels were also determined in CRC cell lines. We collected paired tumor tissue and unchanged mucosa of the large intestine from 121 CRC patients as well as 72 colon biopsies of healthy subjects obtained during screening colonoscopy. PLAGL1 mRNA levels were determined by quantitative PCR, while PLAGL1 protein expression was estimated by western blotting and immunohistochemistry. PLAGL1 mRNA level in tumor tissue was ~2-fold lower than in samples of corresponding unchanged tissues and biopsies of healthy colon mucosa. Downregulated expression of PLAGL1 mRNA was also observed in all tested CRC cell lines. Although the average content of PLAGL1 protein did not differ significantly between tumor and unchanged tissues of CRC patients or colon mucosa of healthy individuals, the decreased PLAGL1 protein levels in tumor specimens correlated with lymph node involvement, the presence of metastases and higher TNM disease stage. The PLAGL1 expression level did not correlate significantly with patient overall survival; however, the hazard ratio for patients whose tumor tissues showed reduced PLAGL1 immunohistochemical staining was twice higher than in patients with increased PLAGL1 immunoreactivity. In conclusion, these results suggest that dysregulation of PLAGL1 expression may be involved to some extent in the progression of CRC, but the so far collected patient survival data do not confirm applicability of the PLAGL1 expression level as a prognostic factor in CRC.
authors.affiliation: Department of Human Histology and Embryology, Faculty of Medical Sciences, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Kowalczyk
authors.affiliation: Department of Human Histology and Embryology, Faculty of Medical Sciences, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
authors.forename: Bartlomiej E
authors.initials: BE
authors.lastname: Krazinski
authors.affiliation: Department of Human Histology and Embryology, Faculty of Medical Sciences, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Godlewski
authors.affiliation: Department of Human Histology and Embryology, Faculty of Medical Sciences, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kiewisz
authors.affiliation: Department of Human Histology and Embryology, Faculty of Medical Sciences, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Kwiatkowski
authors.affiliation: Department of Human Histology and Embryology, Faculty of Medical Sciences, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sliwinska-Jewsiewicka
authors.affiliation: Department of Human Histology and Embryology, Faculty of Medical Sciences, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kiezun
authors.affiliation: Department of Histology, Medical University of Gdansk, 80-210 Gdansk, Poland.
authors.forename: Piotr M
authors.initials: PM
authors.lastname: Wierzbicki
authors.affiliation: In Vitro and Cell Biotechnology Laboratory, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-243 Olsztyn, Poland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bodek
authors.affiliation: Department of Pathomorphology, Faculty of Medical Sciences, University of Warmia and Mazury, 10-561 Olsztyn, Poland.
authors.forename: Marian
authors.initials: M
authors.lastname: Sulik
authors.affiliation: Department of Human Histology and Embryology, Faculty of Medical Sciences, University of Warmia and Mazury, 10-082 Olsztyn, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Kmiec
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C106464:PLAGL1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins