Mouse mammary tumour virus-like virus (MMTV-LV) is present within the liver in a wide range of hepatic disorders and unrelated to nuclear p53 expression or hepatocarcinogenesis

• Published in: Journal of hepatology Vol. 50; no. 3; pp. 548 - 554
• Main Authors: Johal, Harpreet, Marie Scott, Gillian, Jones, Robert, Camaris, Catherine, Riordan, Stephen, Rawlinson, William D
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01-03-2009; Elsevier
• Subjects: Animals; Biliary Atresia - virology; Biological and medical sciences; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Estrogen receptor-alpha (ER-α); Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis - virology; Hepatolenticular Degeneration - virology; Humans; Liver - virology; Liver Cirrhosis - virology; Liver Diseases - virology; Liver Neoplasms - pathology; Liver Neoplasms - virology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Mammary Neoplasms, Experimental - virology; Mammary Tumor Virus, Mouse - genetics; Mammary Tumor Virus, Mouse - isolation & purification; Medical sciences; Mice; Mouse mammary tumour virus-like virus (MMTV-LV); Other diseases. Semiology; p53 tumour suppressor protein; Polymerase Chain Reaction; Primary Biliary Cirrhosis (PBC); Progesterone receptor (PgR); Receptors, Progesterone - genetics; Receptors, Progesterone - metabolism; Transcription, Genetic; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; Viral Envelope Proteins - genetics; p53 tumour suppressor protein; Primary Biliary Cirrhosis (PBC); Progesterone receptor (PgR); Mouse mammary tumour virus-like virus (MMTV-LV); Estrogen receptor-alpha (ER-α); Primary biliary cirrhosis; Liver; p53 Protein; Hepatic disease; Carcinogenesis; Liver cancer; Estrogen receptor-alpha (ER-a); Gastroenterology; Suppressor; Mammary gland; Rodentia; Malignant tumor; Virus; Vertebrata; Mammalia; Mouse; Animal; Breast; Digestive diseases; Cancer; Hormonal receptor
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2008.10.026

Background/Aims The human equivalent of mouse mammary tumour virus (MMTV-LV) may have a role in the pathogenesis of primary biliary cirrhosis (PBC) and breast carcinogenesis. We investigated MMTV-LV prevalence in patients with liver disease of diverse aetiology and associations with hepatic expression of hormonal receptors, p53 protein and complicating hepatocarcinogenesis. Methods Nested PCR for MMTV-LV envelope was performed using tissue from 210 patients with liver disease and 20 patients with histologically normal liver. Hepatic expression of estrogen receptor-alpha (ER-α), progesterone receptor (PgR) and p53 protein was determined by immunohistochemistry. MMTV-LV expression was also determined in hepatocellular carcinoma (HCC) tissue from 21 patients, in 11 of whom paired non-tumourous liver tissue was available for comparison. Results MMTV-LV envelope sequences were present in 25% (53/210) of liver disease biopsies but not in histologically normal liver (0/20) ( P = 0.02). There was no association between MMTV-LV presence and hepatic expression of ER-α or p53 protein. No liver sections were PgR positive. MMTV-LV prevalence was not significantly different in HCC tissue, paired non-tumourous chronic liver disease tissue from the same patients and liver disease tissue from patients without complicating HCC. Conclusions Hepatic expression of MMTV-LV is evident in a wide range of non-cirrhotic and cirrhotic liver diseases, irrespective of ER-α, PgR or p53 status, and unrelated to complicating HCC.