In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 18_suppl ( 2006-06-20), p. 10109-10109
Abstract:
10109 Background: FHL2 belongs to the expanding family of proteins that possess highly conserved double Zn-finger motifs, CX 2 CX 16–23 HX 2 CX 2 CX 2 CX 16–21 CX 2 (C/H/D), and are involved in protein-protein interactions and transcriptional regulation. FHL2 was primarily described as “down regulated in rhabdomyosarcama cells LIM domain protein” (DRAL). Further studies also indicated a connection of FHL2 with the tumor biology. Its expression has been shown to be increased in tumors of epithelial and melanoma cell origin. A recent publication describes the interaction of FHL2 with the breast cancer susceptibility gene 1 (BRCA1) but to date little is known about the function of FHL2 in breast cancer. Methods: Tumor samples of 61 breast cancer patients and 8 normal breast tissues were lysed and subjected to Western blot analysis using a monoclonal FHL2-specific antibody; Tissue specimens of normal breast and breast cancer were histologically examined with the monoclonal antibody used for the Western blot analysis; Luciferase assays were carried out in MCF-7 breast cancer cells, using AP1-dependent reporter plasmids. Anchorage-independent growth was assayed by colony formation in soft agar. Results: FHL2 is overexpressed in almost all human breast cancer tissues tested but not in normal breast tissues and only low levels of FHL2 expression were present in four premalignant ductal carcinoma in situ (DCIS). Co-immunoprecipitation assays and GST-pull down experiments revealed that FHL2 interacts with the proto-oncogene c-jun in breast cancer cells. Reporter gene assays demonstrated that FHL2 represses c-jun-mediated activation of an idealized AP-1-regulated reporter gene in a dose-dependent manner. This repression was also seen on the naturally occurring AP-1-dependent IL2 promoter. The repression domain was identified within the N-terminal half of the FHL2 molecule. Finally, we show that stable expression of FHL2 leads to anchorage-independent growth of breast cancer cells in soft agar. Conclusions: Taken together, our data suggest that by modulating the activity of transcription factors such as c-jun, the expression of FHL2 in breast cancer might contribute to the malignant potential of breast tumors. No significant financial relationships to disclose.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2006.24.18_suppl.10109
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2006
detail.hit.zdb_id:
2005181-5
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