Abstract. The insulin-like growth factor (IGF)-1 gene consists of 6 exons resulting in the expression of 6 variant forms of mRNA (IA, IB, IC, IIA, IIB and IIC) due to an alternative splicing. The mechanisms of IGF-1 gene splicing and the role of local expression manifested by IGF-1 mRNA variants in colorectal carcinoma (CRC) have not been extensively investigated. Therefore, the aim of our study was to analyse the expression of IGF-1 mRNA isoforms [A, B, C, P1 (class I) and P2 (class II)], as well as the protein expression in CRC and control samples isolated from 28 patients. The expression of Ki-67 was also analysed and clinical data were obtained. For this purpose, we used quantitative real-time PCR (qPCR) and immunocytochemistry. The expression of mRNAs coding for all splicing isoforms of IGF-1 was observed in every tissue sample studied, with a significantly lower expression noted in the CRC as compared to the control samples. The cytoplasmic expression of IGF-1 protein was found in 50% of the CRC and in ~40% of the non-tumor tissues; however, no significant quantitative inter-group differences were observed. The expression of the IGF-1 gene in the 2 groups of tissues was controlled by the P1 and P2 promoters in a similar manner. No significant differences were detected in the expression of the IGF-1 A and B isoforms; however, their expression was significantly higher compared to that of isoform C. No significant differences were observed between the expression of Ki-67 mRNA in the CRC and control tissue even though the expression of the Ki-67 protein was higher in the CRC compared to the control samples. Ki-67 protein expression was associated with the macroscopic and microscopic aspects of CRC. A significant positive correlation was found between the local production of total mRNA and isoform A and the expression of Ki-67 mRNA, although only in the non-tumor tissues. In CRC samples, the local expression of the total IGF-1 mRNA and all splicing isoforms of IGF-1 mRNA decreased as compared to the normal colon tissues, although however, with conservation of both gene promoter activities and with the continued principal splicing IGF-1 mRNA isoforms.

IntroductionThe role of Wnt/ β -catenin signaling pathway in HCV-associated hepatocellular carcinogenesis is still unknown.Material and methodsThis study aimed to perform quantitative analysis of immuno- and hybridocytochemical expression of β -catenin, E- and N-cadherins and HCV proteins (C, NS3, NS5A) in long-lasting (≥ 20 years) chronic hepatitis C (CH-C) (n = 54), hepatocellular carcinoma (HCC) (n = 61), and control liver samples (n = 8).ResultsTypical membranous expression of β -catenin in the control liver was higher than in the CH-C and HCC (p = 0.06). The mean β -catenin tissue expression in CH-C was similar to controls, and significantly higher than that of HCC (p = 0.005). E-cadherin expression was lower in CH-C than in the control (p = 0.045) and HCC (p < 0.001). In HCC both β -catenin and E-cadherin expressions were significantly lower in comparison to controls (p = 0.02, p = 0.001, respectively). Positive correlations were found between β -catenin and E-cadherin (in CH-C and HCC), β -catenin and N-cadherin (HCC), E- and N-cadherins expressions (HCC) (p < 0.05 in all cases). In CH-C the positive correlation was demonstrated between NS5A protein and β -catenin, and between the all HCV proteins (C, NS3, NS5A) and E-cadherin expression (p < 0.05 in all cases).ConclusionsAlterations in cellular locations of β -catenin and E-cadherin in CH-C and HCC pointed to structural disturbances in intercellular junctions in the livers and presence of the transcriptionally inactive form of β -catenin. The reduced expression of E-cadherin in long-lasting CH-C may represent an early indicator of the epithelial-mesenchymal transition. The most important role in modulation of the Wnt/ β -catenin pathway in vivo is probably played by the NS5A viral protein.

Background:Several studies have shown increased serum levels of proinflammatory cytokines (Folia Morphol 2015; 74, 1: 65-72)

Differences in quantitative expression of IGF-1 mRNA isoforms in HCV-infected livers, as compared to the control, suggest that HCV may induce alteration of IGF-1 splicing profile.

Aim of the studySeveral epidemiological studies have attempted to demonstrate a relationship between increased serum level of insulin-like growth factor 1 (IGF-1) and an augmented risk of developing colorectal cancers (CRC).The human IGF-1 gene is composed of 6 exons and demonstrated expression of 6 different splice variants (isoforms) of mRNA (IA, IB, IC, IIA, IIB and IIC).The aim of the study was to evaluate the expression of different isoforms of IGF-1 mRNA in CRC and normal colon tissue.Material and methods13 paired tissue specimens (colorectal tumor and non-tumor tissues) were analyzed using both quantitative polymerase chain reaction (PCR) and immunocytochemistry methods (IHC). The expression of classes I and II and variants A, B, C of IGF-1 mRNA were measured.ResultsIn CRC higher amounts of IGF-1 class II mRNA than class I mRNA were detected. Among A, B, C isoforms, A variant of IGF-1 mRNA prevailed. The amounts of IGF-1 class I and class II mRNAs and of IGF-1 variant B mRNA were lowered in CRC as compared to the control. In CRC significant correlations were detected between reciprocal expression of class I and class II as well as between I and II isoforms and A, B and C.ConclusionsExpression of IGF-1 mRNA isoforms differs between normal and CRC tissues. Even if all isoforms of IGF-1 mRNA manifested correlations with each other in tissues of CRC, expression of all transcripts (except that of isoform A) was significantly decreased as compared to the control.