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| 2. |
- Lagergren, Anna, et al.
(författare)
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Neuroblastoma and pre-B lymphoma cells share expression of key transcription factors but display tissue restricted target gene expression
- 2004
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407. ; 4:80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transcription factors are frequently involved in the process of cellular transformation, and many malignancies are characterized by a distinct genetic event affecting a specific transcription factor. This probably reflects a tissue specific ability of transcription factors to contribute to the generation of cancer but very little is known about the precise mechanisms that governs these restricted effects. Methods: To investigate this selectivity in target gene activation we compared the overall gene expression patterns by micro-array analysis and expression of target genes for the transcription factor EBF in lymphoma and neuroblastoma cells by RT-PCR. The presence of transcription factors in the different model cell lines was further investigated by EMSA analysis. Results: In pre-B cells mb-1 and CD19 are regulate by EBF-1 in collaboration with Pax-5 and E-proteins. We here show that neuroblastoma cells express these three, for B cell development crucial transcription factors, but nevertheless fail to express detectable levels of their known target genes. Expression of mb-1 could, however, be induced in neuroblastoma cells after disruption of the chromatin structure by treatment with 5-azacytidine and Trichostatin A. Conclusion: These data suggest that transcription factors are able to selectively activate target genes in different tissues and that chromatin structure plays a key role in the regulation of this activity.
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| 4. |
- Manetopoulos, Christina
(författare)
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Transcriptional networks in neuroblastoma and breast cancer
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Transcription factors of the basic Helix-loop-helix (bHLH) family of proteins are important regulators of cellular processes such as proliferation and differentiation. Many cancer diseases show a block in differentiation, and aberrant regulation of several bHLH factors have been implicated in the development of different malignancies. Neuroblastoma is a childhood tumour that arises in the developing sympathetic nervous system. The cells are blocked at an early stage of differentiation and display an immature phenotype. HEN1 is a bHLH transcription factor important for neuronal development originally isolated from neuroblastoma. We studied HEN1 and its functional interaction with the Lim-only (LMO) proteins in neuroblastoma. We detected a strong interaction between HEN1 and LMO4, and this interaction modulated the HEN1 transcription activity. Furthermore, we found a possible role for HEN1 in neuronal differentiation, however, the significance of this finding needs further experiments. The O/E-protein family also share the HLH motif and functions in neuronal development. In our study on O/E-proteins, we discovered expression of these factors in neuroblastoma. We found that O/E-1 regulate the expression of the important neuronal marker genes SCG10 and Chromogranin A. bHLH factors are also involved in the regulation of proper development of breast tissue. ID2 has been implicated in the development of breast cancer. We studied the ID2 expression in a breast cancer tissue array, where ID2 correlated with a less aggressive tumour phenotype. Furthermore, we studied the relation between the important signalling pathways involving Notch1 and its target gene and ERK1/2 in breast cancer. The results revealed a Notch1-independent regulation of Hes1 and that ERK1/2 signalling might contribute to regulation of Hes1 expression in breast cancer.
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| 5. |
- Persson, Paula, et al.
(författare)
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Olf/EBF proteins are expressed in neuroblastoma cells : potential regulators of the Chromogranin A and SCG10 promoters
- 2004
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Ingår i: International Journal of Cancer. - : Wiley-Liss, Inc.. - 0020-7136 .- 1097-0215. ; 110:1, s. 22-30
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Tidskriftsartikel (refereegranskat)abstract
- The childhood malignancy neuroblastoma is derived from developmentally arrested sympathetic nervous system precursor cells. To obtain further insight into the molecular processes involved in the formation of these tumors, we decided to investigate the functional role of Olf/EBF (O/E) transcription factors in human neuroblastoma cells. We here report that O/E-1 and O/E-2 are expressed at variable levels in neuroblastoma cell lines and that O/E proteins could be identified by electrophoretic mobility shift assays. To identify potential neuronal target genes for O/E proteins in neuroblastoma cells we investigated the ability of a set of neuronal promoters to interact with O/E-1 in electrophoretic mobility shift assays. This analysis suggested that the Chromogranin A (CgA) and SCG10 promoters both contained binding sites for O/E-1. O/E-1 was able to activate the CgA promoter in vivo and mutation of the O/E-1 binding site in the CgA promoter reduced the functional activity of the element to about 60% of the wild-type in neuroblastoma cells, supporting the idea that O/E proteins may be involved in the control of the CgA promoter. Furthermore, overexpression of O/E-1 in hippocampal progenitor cells led to neurite outgrowth, indicative of a role for O/E proteins in neuronal differentiation.
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| 7. |
- Stighall, Maria, et al.
(författare)
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High ID2 protein expression correlates with a favourable prognosis in patients with primary breast cancer and reduces cellular invasiveness of breast cancer cells.
- 2005
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 115:3, s. 403-411
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Tidskriftsartikel (refereegranskat)abstract
- ID proteins have been implicated in the regulation of cell proliferation and differentiation in various cell types during normal development as well as in the formation of cancer. Our aim was to delineate the expression of ID2 by immunohistochemistry in primary breast cancer in order to detect potential associations with cell cycle regulatory proteins and/or clinicopathologic parameters. We further overexpressed ID2 in a breast cancer cell line to elaborate potential effects on proliferation and invasiveness. We observed large variations in ID2 expression in primary breast cancer, and the protein was localised to both the nucleus and cytoplasm. Interestingly, a high cytoplasmic ID2 protein level correlated with a favourable prognosis. Overexpressing ID2 in the MDA-MB-468 breast cancer cell line generated a marked cytoplasmic localisation of the protein and reduced the invasive capacity of cells. Modest enhancement of cell proliferation was further detected in ID2-overexpressing cells. In conclusion, ID2 protein expression varies substantially within primary breast tumours and high cytoplasmic levels of ID2 might reflect a less aggressive breast tumour phenotype.
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