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Please use this identifier to cite or link to this item: http://hdl.handle.net/1783.1/999
Title: 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.
Keywords: Frizzled related protein (Frp)
Wnt-signaling pathway
Rat Frp (rFrp) gene
Invasive breast tumors
Lymph node metastasis
Issue Date: 2001
Citation: Proceedings advanced study institute on molecular genetic basis of cancer, Hong Kong, 6-12 Jan. 2001, HKUST, Hong Kong, 2001, p. 214-223
Abstract: 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.
URI: http://hdl.handle.net/1783.1/999
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