In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 2048-2048
Abstract:
Tissue factor is recognized to be an important regulator of tumor angiogenesis and metastasis, independent of its participation in the blood coagulation pathway. The tissue factor gene is highly expressed only in breast carcinoma cells having high invasive potential, but the mechanisms regulating tissue factor gene expression in breast cancer cells remain unclear. This study examined the hypothesis that microRNA regulation of tissue factor expression is responsible for over-expression of the tissue factor gene in invasive breast cancer cells. Tissue factor was highly expressed in the highly invasive MDA-MB-231 line but was barely detectable in the less invasive MCF-7 line, as assayed by RT-PCR and western blot. A reporter gene assay showed that the tissue factor promoter can be activated in extracts prepared from MCF-7 cells. Forced expression of tissue factor cDNA was achieved in MCF-7 cells, implying that that tissue factor expression is regulated by the 3′-UTR of its transcript. Bioinformatics analysis suggested that microRNA species such as miR-19 (miR-19a and 19b) and miR-106b interact with the 3’-UTR of the tissue factor transcript and may regulate tissue factor protein translation and/or mRNA degradation. microRNA array confirmed that miR-19b is highly expressed in MCF-7 cells, as compared to MDA-MB-231 cells. A reporter gene assay using a TF-3′-UTR-luciferase construct indicated that the tissue factor 3′-UTR negatively regulates tissue factor expression, an effect that was completely reversed by deletion of the miR-19 binding site in the reporter construct. Application of an antisense microRNA for miR-19 enhanced tissue factor expression in MCF-7 cells. This study demonstrates that tissue factor expression in breast cancer cells is regulated by miR-19. The expression pattern of miR-19 in breast cancer tissues and its role in mediating angiogenesis and metastasis merit future investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2048.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-2048
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
