title: Osteopontin expression correlates with nuclear factor-κB activation and apoptosis downregulation in clear cell renal cell carcinoma.
abstract: Osteopontin (OPN) is a phosphoglycoprotein implicated in tumorigenesis and tumor cell metastasis. Apoptosis inhibition is one of the mechanisms that contribute to development and progression of cancer, and might be initiated by OPN interaction with tumor cells. The aim of this study was to analyze the relation between OPN and nuclear factor-kappa B (NF-κB) expression in clear cell renal cell carcinoma (CCRCC), as well as their relation to apoptotic activity of tumor cells. Expression of OPN protein and p65 NF-κB subunit was analyzed immunohistochemically in 87 CCRCC samples, and compared mutually and with apoptotic index. Expression of OPN mRNA was analyzed using quantitative real-time PCR and compared with OPN and NF-κB protein expression in 22 CCRCC samples. Statistical analysis showed an association of p65 NF-κB with OPN mRNA (p=0.015) and protein (p<0.001). Also, we found an inverse relationship of OPN with NF-κB protein expression and apoptotic activity of tumor cells (p=0.006 and p=0.022, respectively). Our results indicate that p65 NF-κB signaling pathway may be involved in OPN-mediated CCRCC progression, partly by protecting tumor cells from apoptosis. Therefore, both molecules can constitute potential targets for therapeutic intervention in CCRCC.
authors.affiliation: Department of Pathology, Rijeka University School of Medicine, Rijeka, Croatia. kmatusan@medri.hr
authors.forename: Koviljka
authors.initials: K
authors.lastname: Matušan-Ilijaš
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
authors.forename: Dora
authors.initials: D
authors.lastname: Fabbro
authors.forename: Gordana
authors.initials: G
authors.lastname: Dorđević
authors.forename: Ita
authors.initials: I
authors.lastname: Hadžisejdić
authors.forename: Maja
authors.initials: M
authors.lastname: Grahovac
authors.forename: Ivana
authors.initials: I
authors.lastname: Marić
authors.forename: Josip
authors.initials: J
authors.lastname: Spanjol
authors.forename: Blaženka
authors.initials: B
authors.lastname: Grahovac
authors.forename: Nives
authors.initials: N
authors.lastname: Jonjić
authors.forename: Ksenija
authors.initials: K
authors.lastname: Lučin
mesh_terms: D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D053495:Osteopontin / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000032:analysis*
chemical_list: C498143:RELA protein, human; D012333:RNA, Messenger; C506895:SPP1 protein, human; D051996:Transcription Factor RelA; D053495:Osteopontin