Genetic disregulation of gene coding tumor necrosis factor alpha receptors (TNFalpha Rs) in colorectal cancer cells.
The expression of TNF ligand by malignant cells might be a mechanism for tumour immune escape. Genetic disregulation of gene coding TNF receptors was observed in neoplastic disease by an increased number of receptors on tumour cells and ligand-receptor activity. It might cause tumour proliferation and metastatic potential. Structure of TNF receptors influences TNF activity in vivo and structure of TNF R2 gene may suggest post-transcription modification based on alternative splicing. The aim of the study was to analyse the expression of gene coding TNF receptors R2 and R2/R7 (without exon 7) by estimation of mRNA expression of colorectal cancer cells in comparison with surrounding tissue free from neoplastic infiltration and searched for differently spliced TNFalphaR2/R7 isoforms. The study included fifty four patients with histopathologically confirmed adenocarcinoma (Stage III according to the AJC TNM Classification). Tissue samples removed from the tumour region were obtained from colorectal cancer patients undergoing surgical treatment. The samples were divided into two parts. The first one--was routinely examined histopathologically, the second one--was used for RNA extraction and the number of TNF and its receptors mRNA copies were subsequently quantified. The TNF and TNFRII genes expression were estimated based on the number of mRNA copies on 1 microg total RNA. The presence of TNFR2 and TNFR2/R7 isoforms in tumour, normal and metastatic cells was observed. The highest number of mRNA TNF copies and over expressed TNF genes were investigated and significantly noticed in metastatic cells (lymph nodes). The decreased number of TNFR2/R7 mRNA copies in metastatic lymph nodes secondarily influenced the decreased TNF soluble receptors' concentration. In conclusion, the genetic disregulation observed in neoplastic disease usually concerns dysfunction of cytokines receptor genes.
Muc-Wierzgon
M
M
Dept. and Teaching Ward of Internal Medicine, Silesian Medical University, Bytom, Poland.
Nowakowska-Zajdel
E
E
Kokot
T
T
Kozowicz
A
A
Zubelewicz
B
B
Klakla
K
K
Mazurek
U
U
Cholewa
K
K
Wilczok
T
T
Wierzgon
J
J
Sosada
K
K
D000230:Adenocarcinoma / Q000378:metabolism; D000328:Adult; D017398:Alternative Splicing; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005091:Exons; D005260:Female; D005456:Fluorescent Dyes / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008207:Lymphatic Metastasis; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D008957:Models, Genetic; D009362:Neoplasm Metastasis; D009696:Nucleic Acids / Q000737:chemistry; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012984:Software
D016207:Cytokines; D005456:Fluorescent Dyes; D008024:Ligands; D009696:Nucleic Acids; D020033:Protein Isoforms; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D012313:RNA