The homeobox gene HLXB9 is upregulated in a morphological subset of poorly differentiated hepatocellular carcinoma

Abstract

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.

MNX1 Is Oncogenically Upregulated in African-American Prostate Cancer

“…MNX1 is a homeobox gene that is known to be an oncogene in the rare malignancy infantile AML (25). It has also been reported to be increased in poorly differentiated hepatocellular carcinoma cell lines (29). It has never been linked to PCa previously, perhaps since most prior molecular genetic studies of PCa have been dominated by EA PCa, where its expression is lower overall.…”

Homeobox Protein HB9 Binds to the Prostaglandin E Receptor 2 Promoter and Inhibits Intracellular cAMP Mobilization in Leukemic Cells

“…Consistency of the gene expression footprint in HLXB9 expressing HL60 cells and blast cells of translocation t(7;12) positive infants directs us to the conclusion that the gene expression signature in translocation t(7;12) positive blast cells is related to the concomitant high HLXB9 expression. The impact of HLXB9 on target gene expression, which is distributed to cell-cell or cell-matrix interactions, is fostered by a recently published study of Wilkens et al (8). They identified the coordinated up-regulation of HLXB9 and genes involved in cell-cell interactions in hepatocellular carcinoma (8).…”

“…The impact of HLXB9 on target gene expression, which is distributed to cell-cell or cell-matrix interactions, is fostered by a recently published study of Wilkens et al (8). They identified the coordinated up-regulation of HLXB9 and genes involved in cell-cell interactions in hepatocellular carcinoma (8).…”

“…Moreover, HLXB9 expression is described in colorectal cancer tissue and hepatocellular carcinoma (7,8). Other than its role in differentiation of tissues from the endoderm and ectoderm, the function of HB9 in derivates from the mesenchyme, like hematopoietic cells, is largely unknown.…”

A Novel Three-Colour Fluorescence in Situ Hybridization Approach for the Detection of t(7;12)(q36;p13) in Acute Myeloid Leukaemia Reveals New Cryptic Three Way Translocation t(7;12;16)

“…Overexpression of HLXB9 has been recently reported in other forms of cancers, such as colorectal cancer and hepatocellular carcinoma, suggesting a common pathway of oncogenesis [16,17]. …”