1. Gene and protein expression of mTOR and LC3 in hepatocellular carcinoma, colorectal liver metastasis and 'normal' liver tissues
- Author
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Clara Benna, Alessandra Comparato, Salvatore Pucciarelli, Andrea Errico, Isacco Maretto, Marina Bortolami, Fabio Farinati, and Umberto Cillo
- Subjects
0301 basic medicine ,Male ,Cirrhosis ,Colorectal cancer ,Protein Expression ,Cancer Treatment ,Gene Expression ,medicine.disease_cause ,mTOR, LC3, p62, HCC, autophagy ,Metastasis ,0302 clinical medicine ,Gene expression ,Basic Cancer Research ,LC3 ,Medicine and Health Sciences ,Tumor Microenvironment ,HCC ,Phosphorylation ,Multidisciplinary ,Cell Death ,Liver Diseases ,TOR Serine-Threonine Kinases ,p62 ,Liver Neoplasms ,Middle Aged ,Gene Expression Regulation, Neoplastic ,Surgical Oncology ,Oncology ,Cell Processes ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,mTOR ,Medicine ,Female ,Colorectal Neoplasms ,Microtubule-Associated Proteins ,Research Article ,Clinical Oncology ,Adult ,autophagy ,Carcinoma, Hepatocellular ,Science ,Autophagic Cell Death ,Down-Regulation ,Gastroenterology and Hepatology ,Research and Analysis Methods ,Diagnosis, Differential ,03 medical and health sciences ,Gastrointestinal Tumors ,medicine ,Gene Expression and Vector Techniques ,Genetics ,Humans ,Molecular Biology Techniques ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Aged ,Colorectal Cancer ,Molecular Biology Assays and Analysis Techniques ,business.industry ,Autophagy ,Carcinoma ,Cancers and Neoplasms ,Biology and Life Sciences ,Hepatocellular Carcinoma ,Cell Biology ,medicine.disease ,030104 developmental biology ,Case-Control Studies ,Cancer research ,Clinical Medicine ,Carcinogenesis ,business - Abstract
The physiological role of autophagy in the progression of liver diseases is still debated. To understand the clinical relevance of autophagy in primary e secondary hepatic tumors, we analyzed the expression of mTOR (mammalian target of rapamycin), a key regulator of autophagy; Raptor (regulatory-associated protein of mTOR); ULK1 (Unc-51 like kinase 1) determinant in the autophagy initiation; LC3 (microtubule-associated protein 1A/1B-light chain 3), a specific marker of autophagosomes; and p62, a selective autophagy receptor. Samples from subjects with chronic hepatitis (n.58), cirrhosis (n.12), hepatocellular carcinoma (HCC, n.56), metastases (n.48) from colorectal cancer and hyperplasia or gallbladder stones (n.7), the latter considered as controls, were examined. Gene expression analysis was carried out in n.213 tissues by absolute q-PCR, while protein expression by Western Blot in n.191 lysates, including tumoral, surrounding tumoral and normal tissues. Nonparametric statistical tests were used for comparing expression levels in the above-mentioned groups. Subgroup analysis was performed considering viral infection and chemotherapy treatment. The mTOR transcriptional level was significantly lower in metastases compared to HCC (P = 0.0001). p-mTOR(Ser2448) and LC3II/LC3I protein levels were significantly higher in metastases compared to HCC (P = 0.008 and PConclusions:the different expression of proteins considered, owning their interaction and diverse tissue microenvironment, indicate an impairment of the autophagy flux in primary liver tumors that is critical for the promotion of tumorigenesis process and a coexistence of autophagy inhibition and activation mechanisms in secondary liver tumors. Differences in mTOR and LC3 transcripts emerged in tumor-free tissues, therefore particular attention should be considered in selecting the control group.
- Published
- 2020