Disease relevance of DIRC2

• Through a subsequent positional cloning effort we found that this breakpoint targets a hitherto unidentified gene, designated DIRC2 (disrupted in renal cancer 2) [1].
• To understand the role of NO under hypoxia we made use of pVHL-deficient renal carcinoma cells (RCC4) that show a high steady state HIF-1alpha expression under normoxia [2].
• Despite this robust interaction, analysis of the PMA-induced proteasome-dependent degradation of PKCdelta in different RCC (renal cell carcinoma) lines (RCC4, UMRC2 and 786 O) shows that there is no correlation between the degradation of PKCdelta and the presence of active pVHL [3].
• Two of the three compounds were cell type specific, whereas compound DJ12 inhibited VEGF at subtoxic levels in breast cancer cell lines MDA-468 and ZR-75, melanoma cell line MDA-435, and pVHL mutant renal cancer cell lines RCC4 and 786-0 [4].

High impact information on DIRC2

• Exposing RCC4 cells to hypoxia in combination with the NO donor DETA-NO (2,2'-(hydroxynitrosohydrazono) bis-ethanimine), but not hypoxia or DETA-NO alone, decreased HIF-1alpha protein and attenuated HIF-1 transactivation [2].
• Ang-2 gene expression was down-regulated by hypoxia in VHL wild-type RCC786-0 and RCC4 transfectants (p = 0.0002 and p = 0.04, respectively), mirroring the low expression in human tumour cells [5].
• Positional cloning of the chromosome 3 breakpoint led to the identification of a novel gene, DIRC2, that spans this breakpoint [6].
• Expression of the von Hippel-Lindau (VHL) tumor suppressor factor blocked the expression of both FECH mRNA and HIF-1alpha protein during normoxic culture of renal carcinoma cell line (RCC4) [7].
• To evaluate whether DIRC2 is also targeted in sporadic RCC cases with cytogenetically defined 3q21 breakpoints, fluorescence in situ hybridization analysis was performed on metaphase spreads and/or interphase nuclei of 12 primary sporadic RCC using genomic clones from a 3q21 breakpoint-spanning contig as probes [8].

Anatomical context of DIRC2

• The effect of the von Hippel-Lindau (VHL) gene and hypoxia in the renal cell lines RCC786-0 and RCC4 has also been investigated [5].

Analytical, diagnostic and therapeutic context of DIRC2

• No significant difference was found in the incidence of extra-pseudocapsule cancer lesions between the tumors 2.5 cm or less and that greater than 2.5 cm.CONCLUSIONS: These data suggest that when partial nephrectomy is performed in RCC 4 cm or less, a 10mm margin may be too large and go against renal function maintaining [9].

References