Cancer Res：恶性黑色素瘤的新疗法被发现

生物谷

生物谷报道：恶性黑色素瘤是一种源自黑素细胞的恶性肿瘤，它的发病过程已得到很好的阐明，但是传统的疗法对于治疗恶性黑色素瘤收效甚微，只有在转移灶发生前进行的治疗才有疗效。。最近，一系列报道发现，转录因子HOX家族成员在黑色素瘤中被降解，因此有可能是维持黑色素瘤增殖的关键因子。

在最新的一期《癌症研究》杂志上，Surrey大学研究生院的研究者们他们开发出了新的药物HXR9,其可阻断已知HOX家族的一组基因的活性.该项计划领导者Richard Morgan博士称HOX基因在胚胎时期对决定细胞和组织的性质很重要,但它们在癌细胞也能表达.HXR9以高特异性的方式阻断HOX的活性来杀死癌细胞。HXR9在治疗恶性黑色素瘤,肺癌,前列腺癌和肾癌上显示出了特殊疗效。这一研究为癌症的治愈开发出了新的治疗措施，具有重要的现实意义和应用前景。

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).

原文出处：

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

相关基因：

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