Hepatitis A virus receptor blocks cell differentiation and is overexpressed in clear cell renal cell carcinoma

Autor: Anna Meseguer, Joaquim Bellmunt, Margarita Nadal, Maya R. Vilà, Joan Morote, Ruth Porta, Dino A. Feigelstock, Gerardo G. Kaplan
Rok vydání: 2004
Předmět:
Male
Pathology
Cellular differentiation
Cell
Gene Expression
medicine.disease_cause
Polymerase Chain Reaction
Chlorocebus aethiops
Hepatitis A Virus Cellular Receptor 1
RNA
Neoplasm
Receptor
In Situ Hybridization
Fluorescence
Aged
80 and over
Confluency
Membrane Glycoproteins
Chromosome Mapping
Cell Differentiation
Transfection
differentiation
DNA
Neoplasm
Middle Aged
Kidney Neoplasms
kidney tumors
medicine.anatomical_structure
Nephrology
tumor markers
Clear cell carcinoma
Chromosomes
Human
Pair 5
Receptors
Virus
Female
Cell Division
Adult
medicine.medical_specialty
proximal tubule cells
Biology
Cell Line
Tumor
medicine
Animals
Humans
RNA
Messenger
Carcinoma
Renal Cell
Aged
Base Sequence
ccRCC
medicine.disease
Clear cell renal cell carcinoma
RAP-PCR
hhavcr-1
Cancer research
Hepatitis A virus
Carcinogenesis
Zdroj: Kidney international. 65(5)
ISSN: 0085-2538
Popis: Hepatitis A virus receptor blocks cell differentiation and is overexpressed in clear cell renal cell carcinoma. Background The molecular mechanisms underlying tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC) are not well understood. We aimed to identify new molecular markers to provide insight into these processes. Methods This work reports on the identification of human hepatitis A virus cellular receptor 1 (hHAVcr-1) as a differentially expressed gene in ccRCC using RNA-based arbitrarily primed polymerase chain reaction (RAP-PCR). Results were further confirmed by Northern and Western blot assays. Carcinoma 769-P and normal HK-2 cells derived from proximal tubule epithelial cells, grown under different culture conditions, were used to understand the putative role of hHAVcr-1 in renal malignancy. hHAVcr-1 stable transfected clones and dipeptidyl peptidase IV (DPPIV) assays allowed assessing its involvement in cell differentiation. Results The hHAVcr-1 is overexpressed in eight out of 13 ccRCC and its expression neglected in benign oncocytomas. In culture, hhavcr-1 is dramatically overexpressed in normal and tumor cell lines that, having acquired the fully differentiated phenotype, are induced to de-differentiate by means of phorbol ester phorbol 12-myristate-13-acetate (PMA) treatment. Similarly, differentiation prevention by addition of PMA to confluent cells also increases hhavcr-1 expression. hHAVcr-1 stable transfected 769-P cells proved that hhavcr-1 itself blocks differentiation. Since hhavcr-1 is expressed at higher levels in tumor cells, we used an African green monkey cell model to show that immunotoxins directed against the monkey homologue of hhavcr-1 could kill kidney cells. Conclusion Our results showed that hHAVcr-1 blocks differentiation of proximal tubule epithelial cells and that it could be used as a target for therapy of kidney carcinomas.
Databáze: OpenAIRE
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