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Cloning, characterization and functional analysis of the rat frizzled related protein

Authors Hsiao, W. L. Wendy
Yam, Judy W.P.
Wong, Sze Chuen
Chan, Koon Wing
Lee, King Chung
Chan, John K.C.
Issue Date 2001
Source Proceedings advanced study institute on molecular genetic basis of cancer, Hong Kong, HKUST, Hong Kong , 6-12 Jan. 2001, p. 214-223
Summary Frizzled related protein (Frp) is a new family of secreted proteins that contain a region homologous to the extracellular cysteine-rich domain of the frizzled family proteins. The functional role of Frp is far from clear. A few studies have indicated that Frp may play a role in modulating the Wnt-signaling pathway. In our previous study, a rat Frp (rFrp) gene was found to be differentially expressed in Rat 6 fibroblasts overexpressing p53va1135 (R6#13-8). The rFrp gene was otherwise silent in normal parental Rat 6 cells. To elucidate the molecular basis of the transcriptional activation of rFrp, we have isolated and analyzed a 2-kilobase pair promoter region of the rFrp gene. The rFrp gene contains a TATA box and multiple initiation sites. The proximal promoter region contains DNA binding motifs of MZF1, Lyf-1. GATA, IK2, and STAT3 transcriptional factors, which regulate mostly hematopoietic-restricted genes; and SRY and SOX-5 binding motifs known to be involved in sex-determination. Reporter assays and mobility shift assays revealed that the core nucleotides TTTGGGGG in -196 to -189 and GATGATGT in -149 to -142 play a critical role in regulating rFrp expression. In our study, we also demonstrated that rFrp was down regulated in the majority of human invasive breast tumors. The down-regulation of rFrp seemed to correlate with high incidence of lymph node metastasis in breast cancer.
Language English
Format Conference paper
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