Disease relevance of HOXC8

• Overexpression of HOXC8 in LNCaP prostate cancer cells suppressed transactivation by androgen receptors [1].
• In order to analyze the self-delivery activity of Hoxc8, recombinant Hoxc8 protein (rHoxc8) was designed to be expressed and purified in E. coli as a glutathione S-transferase and green fluorescent protein-fused form (GST-GFP-Hoxc8) [2].

High impact information on HOXC8

• Hoxc-8 induces Smad6 binding to DNA as a transcriptional complex [3].
• Glutathione S-transferase-Hoxc-8 protein binds to these two Hox sites specifically [4].
• HOX3 contains at least 7 homeoboxes in 160 kb on chromosome 12 [5].
• RESULTS: Out of the three human prostate cancer cell lines tested, DU-145 and PC3 but not LNCaP cells expressed detectable amount of HOXC8 transcripts [6].
• Overexpression of the homeobox gene HOXC8 in human prostate cancer correlates with loss of tumor differentiation [6].

Chemical compound and disease context of HOXC8

• In situ hybridization was performed with the use of an HOXC8 anti-sense digoxigenin-labeled probe to investigate HOXC8 mRNA expression in 27 prostate cancer tissue specimens [6].

Biological context of HOXC8

• CONCLUSIONS: Our data showing that HOXC8 overexpression is associated with the loss of tumor differentiation in human prostate cancer suggests that HOXC8 may play a role in the acquisition of the invasive and metastatic phenotype of this malignancy [6].
• Chromatin immunoprecipitation experiments reveal that binding of menin to the Hoxc8 locus is not affected by phosphorylation on Ser(543) or Ser(583) [7].
• The finished sequence from BAC clones from the genome of the sea urchin, Strongylocentrotus purpuratus, reveals a gene order wherein the anterior genes (Hox1, Hox2 and Hox3) lie nearest the posterior genes in the cluster such that the most 3' gene is Hox5 [8].
• Using a panel of feline x rodent somatic cell hybrids, the HOX3A locus was assigned to feline chromosome B4 [9].
• The nucleotide sequence similarity of the feline homeobox was 96% to human HOX3A, 94% to mouse Hox-3.1, and 94% to rat R4 [9].

Anatomical context of HOXC8

• Interestingly, this pattern is conserved in the transformed keratinocytes (SiHa cells) except for the appearance of HOXC5 and HOXC8 mRNA [10].
• METHODS: RT-PCR and in situ hybridization experiments were performed to investigate the expression and cell type localization of HOXC8 transcripts in human prostate cancer cell lines and tissues [6].
• Results from in situ hybridization experiments demonstrated that HOXC8 gene was expressed mainly in malignant epithelial cells [6].
• We have previously shown that HOXC8 expression was selectively turned on in human cervix cancer cells compared with normal keratinocytes, suggesting that HOXC8 may be involved in the process leading to the transformation of cervix keratinocytes [Alami et al.: Biochem Biophys Res Commun 257:738-745, 1999] [6].
• Efficient cellular uptake of recombinant murine Hoxc8 homeoprotein in COS-7 cells [2].

Physical interactions of HOXC8

• Smad1 and Smad6 interact with Hoxc8 and regulate its repression activities [11].

Other interactions of HOXC8

• Our data add weight to the body of evidence attributing to a specific adult tissue a particular combination of expressed HOX genes and suggest that HOXC5 and/or HOXC8 could be involved in the process leading to the transformation of cervical keratinocytes [10].
• The interaction between Smad6 and Hoxc-8 was identified by a yeast two-hybrid approach and further demonstrated by co-immunoprecipitation assays in cells [12].
• To determine the usefulness of this sequence for phylogenetic comparisons, we sequenced an 800-bp fragment of the Hoxc9-Hoxc8 intergenic region from several species belonging to different mammalian clades [13].

Analytical, diagnostic and therapeutic context of HOXC8

• The HOXC5 and HOXC8 expression was also observed in two other transformed keratinocytes cell lines of independent origins, Eil-8 and 18-11S3, and confirmed by in situ hybridization [10].

References