Browsing by Subject "Cell surface receptor"

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Open Access
Quantification of SLIT-ROBO transcripts in hepatocellular carcinoma reveals two groups of genes with coordinate expression
(BioMed Central, 2008) Avci, M. E.; Konu, O.; Yagci, T.
Background: SLIT-ROBO families of proteins mediate axon pathfinding and their expression is not solely confined to nervous system. Aberrant expression of SLIT-ROBO genes was repeatedly shown in a wide variety of cancers, yet data about their collective behavior in hepatocellular carcinoma (HCC) is missing. Hence, we quantified SLIT-ROBO transcripts in HCC cell lines, and in normal and tumor tissues from liver. Methods: Expression of SLIT-ROBO family members was quantified by real-time qRT-PCR in 14 HCC cell lines, 8 normal and 35 tumor tissues from the liver. ANOVA and Pearson's correlation analyses were performed in R environment, and different clinicopathological subgroups were pairwise compared in Minitab. Gene expression matrices of cell lines and tissues were analyzed by Mantel's association test. Results: Genewise hierarchical clustering revealed two subgroups with coordinate expression pattern in both the HCC cell lines and tissues: ROBO1, ROBO2, SLIT1 in one cluster, and ROBO4, SLIT2, SLIT3 in the other, respectively. Moreover, SLIT-ROBO expression predicted AFP-dependent subgrouping of HCC cell lines, but not that of liver tissues. ROBO1 and ROBO2 were significantly up-regulated, whereas SLIT3 was significantly down-regulated in cell lines with high-AFP background. When compared to normal liver tissue, ROBO1 was found to be significantly overexpressed, while ROBO4 was down-regulated in HCC. We also observed that ROBO1 and SLIT2 differentiated histopathological subgroups of liver tissues depending on both tumor staging and differentiation status. However, ROBO4 could discriminate poorly differentiated HCC from other subgroups. Conclusion: The present study is the first in comprehensive and quantitative evaluation of SLIT-ROBO family gene expression in HCC, and suggests that the expression of SLIT-ROBO genes is regulated in hepatocarcinogenesis. Our results implicate that SLIT-ROBO transcription profile is bi-modular in nature, and that each module shows intrinsic variability. We also provide quantitative evidence for potential use of ROBO1, ROBO4 and SLIT2 for prediction of tumor stage and differentiation status.
Open Access
Redundant expression of canonical Wnt ligands in human breast cancer cell lines
(Spandidos Publications Ltd., 2006) Benhaj, K.; Akcali, K. C.; Ozturk, M.
Human breast cancer displays nuclear accumulation of β-catenin and induction of cyclin D1 expression, which suggests that canonical Wnt/β-catenin signaling is activated. In other cancers, the activation of canonical wnt/β-catenin signaling is associated with APC, CTNNB1 or AXIN1 mutations. However, these mutations are rare or absent in breast cancer. In search of alternative mechanisms, we performed comprehensive expression analysis of Wnt signaling molecules, including 19 Wnt ligands, ten Frizzled receptors, two co-receptors and four Lef/TCF transcription factors in immortalized normal human mammary epithelial cells (HMEC) and six breast cancer cell lines. HMEC expressed all Frizzled receptors except FZD9 and FZD10. They also expressed LRP5 and LRP6 co-receptors, as well as four Lef/TCF transcription factors. HMEC cells also expressed many Wnt ligands, including WNT1, WNT2B, WNT3, WNT5A, WNT5B, WNT7B, WNT9A, WNT10B and WNT16 . Redundant expression of Wnt ligands, Frizzled receptors, co-receptors and Lef/TCF transcription factors was maintained in breast cancer cell lines with some exceptions. The most important changes in cancer cell lines concerned Wnt ligand expression. We noticed that most breast cancer cell lines overexpressed WNT3A, WNT4, WNT6, WNT8B, WNT9A and WNT10B. In contrast, the expression of WNT5A, WNT5B and WNT16 was usually down-regulated. It is noteworthy that all six Wnt ligands that are overexpressed in malignant cell lines are known to signal through the canonical Wnt/β-catenin signaling pathway, whereas down-regulated WNT5A and WNT5B ligands signal via the non-canonical pathway. The expression of both canonical Wnt ligands and most Frizzled receptors in breast cancer cell lines suggests that canonical Wnt/β-catenin signaling is activated in these cell lines by an autocrine/paracrine mechanism. In support of this prediction, we observed nuclear β-catenin accumulation and cyclin D1 induction in breast cancer cell lines, but not in HMEC. These results imply that ligand-dependent canonical Wnt/β-catenin signaling is active in human breast cancer.