Comparative Immunohistochemical Analysis of Ochratoxin A Tumourigenesis in Rats and Urinary Tract Carcinoma in Humans; Mechanistic Significance of p-S6 Ribosomal Protein Expression

Toxins

Patrycja Gazinska²  Diana Herman³  Cheryl Gillett⁴  Sarah Pinder¹ 

[1] Department of Research Oncology, Guy’s Hospital, King’s Health Partners AHSC, King’s College London School of Medicine, London SE1 9RT, UK;Breakthrough Breast Cancer Research Unit, Guy’s Hospital, King’s Health Partners AHSC, King’s College London School of Medicine, London SE1 9RT, UK;Pathology Department, County Hospital Timisoara, Timisoara 300736, Romania;Breast Tissue and Databank, Guy’s Hospital, King’s Health Partners AHSC, King’s College London School of Medicine, London SE1 9RT, UK;

关键词: ochratoxin A;    phospho-S6 ribosomal protein;    mycotoxin;    renal cell carcinoma;    transitional cell carcinoma;    testicular cancer;    angiosarcoma;    Balkan endemic nephropathy;    food safety;    DNA adducts;   

DOI  :  10.3390/toxins4090643

来源: mdpi

【 摘 要 】

Ochratoxin A (OTA) is considered to be a possible human urinary tract carcinogen, based largely on a rat model, but no molecular genetic changes in the rat carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker indicating activity of the mammalian target of rapamycin, which is a serine/threonine kinase with a key role in protein biosynthesis, cell proliferation, transcription, cellular metabolism and apoptosis, while being functionally deregulated in cancer. To assess p-S6 expression we performed immunohistochemistry on formalin-fixed and paraffin-embedded tumours and normal tissues. Marked intensity of p-S6 expression was observed in highly proliferative regions of rat renal carcinomas and a rare angiosarcoma, all of which were attributed to prolonged exposure to dietary OTA. Only very small OTA-generated renal adenomas were negative for p-S6. Examples of rat subcutaneous fibrosarcoma and testicular seminoma, as well as of normal renal tissue, showed no or very weak positive staining. In contrast to the animal model, human renal cell carcinoma, upper urinary tract transitional cell carcinoma from cases of Balkan endemic nephropathy, and a human angiosarcoma were negative for p-S6. The combined findings are reminiscent of constitutive changes in the rat tuberous sclerosis gene complex in the Eker strain correlated with renal neoplasms, Therefore rat renal carcinogenesis caused by OTA does not obviously mimic human urinary tract tumourigenesis.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.