生物谷報(bào)道：惡性黑色素瘤是一種源自黑素細(xì)胞的惡性腫瘤,，它的發(fā)病過程已得到很好的闡明，但是傳統(tǒng)的療法對(duì)于治療惡性黑色素瘤收效甚微,，只有在轉(zhuǎn)移灶發(fā)生前進(jìn)行的治療才有療效,。。最近,，一系列報(bào)道發(fā)現(xiàn),，轉(zhuǎn)錄因子HOX家族成員在黑色素瘤中被降解，因此有可能是維持黑色素瘤增殖的關(guān)鍵因子,。
在最新的一期《癌癥研究》雜志上,，Surrey大學(xué)研究生院的研究者們他們開發(fā)出了新的藥物HXR9,其可阻斷已知HOX家族的一組基因的活性.該項(xiàng)計(jì)劃領(lǐng)導(dǎo)者Richard Morgan博士稱HOX基因在胚胎時(shí)期對(duì)決定細(xì)胞和組織的性質(zhì)很重要,但它們?cè)诎┘?xì)胞也能表達(dá).HXR9以高特異性的方式阻斷HOX的活性來殺死癌細(xì)胞,。HXR9在治療惡性黑色素瘤,肺癌,前列腺癌和腎癌上顯示出了特殊療效。這一研究為癌癥的治愈開發(fā)出了新的治療措施,，具有重要的現(xiàn)實(shí)意義和應(yīng)用前景,。
Figure 1. The specificity of hexapeptide action. A, HXR9 blocks the binding of HOXD9 to PBX. B16 murine melanoma cells were treated with 60 µmol/L of HXR9 or CXR9 for 4 h. Protein was then extracted from these cells using standard methods, and PBX proteins were precipitated using an anti-PBX antibody. Precipitates were probed for HOXD9, GR, and PBX. HXR9 blocks the binding of PBX to HOXD9 but not to GR. B, HXR9 prevents the formation of HOX/PBX/DNA complexes in cultured B16 cells. Double-stranded oligodeoxynucleotide probes were incubated in protein extracted from B16 cells. One of these probes (HP) contained a HOX/PBX consensus binding region (in boldface)—5' CTGTTTGATT TATTTGTTTA 3'. A second, control probe (HPC) contained an altered HOX/PBX binding site that was not predicted to bind HOX and PBX proteins—5' CTGTTACTGA CGATTGTTTA 3'. The cells were treated for 2 h with 60 µmol/L of HXR9 (H) or with 60 µmol/L of CXR9 (C), or were untreated (U). Protein extracted from cells treated with the control CXR9 peptide caused a mobility shift in HP (lane 2) that could be abolished by 25-fold excess unlabeled HP (lane 8), and enhanced (supershifted) by anti-PBX antibody (lane 14). This supershift was abolished by the inclusion of a blocking peptide that prevented anti-PBX antibody from binding to PBX (lanes 16–18). The mobility of HPC was unchanged by incubating with the protein extract (lane 11). Protein extracted from HXR9-treated cells did not change the mobility of HP (lane 3) or HPC (lane 12), and the mobility of HP was also unchanged in response to unlabeled probe (lane 9) or anti-PBX antibody (lane 15). C, HXR9 prevented the formation of HOX/PBX/DNA complexes in tumors. Tumors injected with HXR9 or CXR9 (10 mg/kg) were used to make cell-free lysates for band shift experiments. The lanes are labeled as above (B). D, HXR9 enters the cytoplasm and nuclei of B16F10 cells in vitro. B16F10 cells were incubated with 60 µmol/L of HXR9 for 2 h and then stained using either an anti-HXR9 antibody labeled with the FITC fluorescent probe (green, Anti-HXR9-FITC), with Hoechst (blue, Hoechst), or with a combination (Combined). As a negative control, B16F10 cells that had not been treated with HXR9 were also stained with anti-HXR9-FITC (No HXR9).
原文出處：
Cancer Research June 15 2007, Volume 67, Issue 12
Antagonism of HOX/PBX Dimer Formation Blocks the In vivo Proliferation of Melanoma
Richard Morgan, Patricia Macanas Pirard, Liesl Shears, Jastinder Sohal, Ruth Pettengell, and Hardev S. Pandha
Cancer Res 2007 67: 5806-5813. doi: 10.1158/0008-5472.CAN-06-4231 [Abstract] [Full Text] [PDF] Supplementary Data
相關(guān)基因：
HOXA1
Official Symbol HOXA1 and Name: homeobox A1 [Homo sapiens]
Other Aliases: BSAS, HOX1, HOX1F, MGC45232
Other Designations: HOX A1 homeodomain protein; Hox 1.6-like protein; homeo box A1; homeobox 1F; homeobox protein HOX-A1; lab-like protein
Chromosome: 7; Location: 7p15.3
Annotation: Chromosome 7, NC_000007.12 (27102149..27099136, complement)
MIM: 142955
GeneID: 3198
