Institute of Pathology, University of Bern, Murtenstrasse 10, Bern, Switzerland.
Virchows Arch. 2011 Jun;458(6):697-708. doi: 10.1007/s00428-011-1070-5. Epub 2011 Apr 12.
The prognostic outcome for hepatocellular carcinoma (HCC) remains poor. Disease progression is accompanied by dedifferentiation of the carcinoma, a process that is not well understood. The aim of this study was to get more insight into the molecular characteristics of dedifferentiated carcinomas using high throughput techniques. Microarray-based global gene expression analysis was performed on five poorly differentiated HCC cell lines compared with non-neoplastic hepatic controls and a set of three cholangiolar carcinoma (CC) cell lines. The gene with the highest upregulation was HLXB9. HLXB9 is a gene of the homeobox genfamily important for the development of the pancreas. RT-PCR confirmed the upregulation of HLXB9 in surgical specimens of carcinoma tissue, suggesting its biological significance. Interestingly, HLXB9 upregulation was primary observed in poorly differentiated HCC with a pseudoglandular pattern compared with a solid pattern HCC or in moderate or well-differentiated HCC. Additional the expression of translated HLXB9, the protein HB9 (NCBI: NP_001158727), was analyzed by western blotting. Expression of HB9 was only detected in the cytoplasm but not in the nuclei of the HCC cells. For validation CC were also investigated. Again, we found an upregulation of HLXB9 in CC cells accompanied by an expression of HB9 in the cytoplasms of these tumor cells, respectively. In conclusion, homeobox HLXB9 is upregulated in poorly differentiated HCC with a pseudoglandular pattern. The translated HB9 protein is found in the cytoplasm of these HCC and CC. We therefore assume HLXB9 as a possible link in the understanding of the development of HCC and CC, respectively.
肝细胞癌 (HCC) 的预后仍然很差。疾病的进展伴随着癌细胞的去分化，这一过程还不是很清楚。本研究的目的是利用高通量技术更深入地了解去分化癌的分子特征。对五个低分化 HCC 细胞系与非肿瘤性肝对照和三个胆管细胞癌 (CC) 细胞系进行了基于微阵列的全基因表达分析。上调最明显的基因是 HLXB9。HLXB9 是同源盒基因家族的一个基因，对胰腺的发育很重要。RT-PCR 证实了 HLXB9 在癌组织手术标本中的上调，表明其具有生物学意义。有趣的是，HLXB9 的上调主要观察到具有假腺泡模式的低分化 HCC 中，与实体模式 HCC 或中或高分化 HCC 相比。此外，还通过 Western blot 分析了翻译的 HLXB9 蛋白 HB9（NCBI：NP_001158727）的表达。HB9 在 HCC 细胞的细胞质中而不是细胞核中表达。为了验证，还研究了 CC。同样，我们发现 CC 细胞中 HLXB9 的上调，伴随着这些肿瘤细胞细胞质中 HB9 的表达。因此，我们假设 HLXB9 可能是理解 HCC 和 CC 各自发展的一个可能的联系。
