engleski

Osteopontin expression correlates with nuclear factor-κB activation and apoptosis downregulation in clear cell renal cell carcinoma

Osteopontin (OPN) is a phosphoglycoprotein implicated in tumourigenicity and tumour cell metastasis. Apoptosis inhibition is one of mechanisms that contribute to development and progression of cancer and might be initiated by OPN interaction with tumour cell. The aim of this study was to establish the relation between OPN and nuclear factor-kappa B (NF-κB) expression at protein and mRNA level in specimens of clear cell renal cell carcinoma (CCRCC), and their relation to apoptosis. Expression of OPN protein and p50/65 NF-κB subunits was analysed immunohistochemicaly in 94 CCRCC samples and compared mutually and to apoptotic index. Expression of OPN mRNA was analysed using quantitative real-time PCR and compared to OPN and NF-κB protein expression in 22 CCRCC samples. Statistical analysis showed the correlation of OPN expression at protein (p<0.001) and mRNA levels (p=0.019) with NF-κB activation, as well as the inverse association with apoptotic rate (p=0.024). Also, activation of both NF-κB subunits showed inverse correlation with apoptotic index (p=0.003). Our data indicate that activation of NF-kB signalling pathway contributes to OPN-mediated CCRCC progression, partly by mediating prosurvival effect on tumour cells. Therefore, both molecules can constitute potential targets for therapeutic intervention in CCRCC.

apoptosis; carcinoma; renal cell; nuclear factor kappa B; osteopontin

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