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PMID:11793365

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Citation

Wong, SC, Lo, SF, Lee, KC, Yam, JW, Chan, JK and Wendy Hsiao, WL (2002) Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours. J. Pathol. 196:145-53

Abstract

Frizzled-related protein (Frp) is a new family of secreted proteins that contain a region homologous to the extracellular cysteine-rich domain (CRD) of the frizzled family proteins. The role of Frp protein is far from clear. To explore the role of Frp and its relationship to the Wnt-signalling pathway in breast cancer, in situ hybridization and immunohistochemical analyses of Frp, Wnt-1, APC, beta-catenin, and its target genes c-myc and cyclin D1 were conducted in 70 specimens of invasive ductal carcinomas of the human breast. Frp mRNA was down-regulated in 62 and elevated in eight tumour specimens, compared with adjacent normal tissues. In the course of tumour progression, however, Frp mRNA steadily increased in both tumour and the adjacent tissues. Interestingly, the number of cases with axillary lymph node metastasis was significantly lower in the group with elevated Frp than in the group with decreased Frp, suggesting that Frp may contribute as a prognostic factor in invasive breast cancer. Wnt-1, a gene implicated in human breast cancer, was markedly elevated in grade 1 tumours, but declined as tumour grade declined. The level of Wnt-1 was linearly correlated with its downstream target beta-catenin (p<0.05), but was inversely correlated with Frp (p<0.05), suggesting a possible negative regulatory role of Frp with regard to Wnt-1. APC was inversely correlated with beta-catenin (p<0.05). Beta-catenin, a key transcriptional activator responsible for the activation of both c-myc and cyclin D1 in colorectal tumours, was detected at high levels in the plasma membranes of cells in normal tissue. In tumour masses, however, beta-catenin lost its tight association with the membrane and diffused into the cytoplasm. Surprisingly, it clearly did not penetrate the nuclei, despite the fact that both c-myc and cyclin D1 were markedly elevated in all tumour tissues. As revealed in this study, Wnt-1/beta-catenin plays very different roles in the oncogenesis of breast and colon cancers. This first systemic analysis of the Frp and the Wnt-signalling pathway in human breast cancer provides a springboard for further work on the role of Frp in the development of breast cancer.

Links

PubMed Online version:10.1002/path.1035

Keywords

Adenomatous Polyposis Coli Protein/analysis; Breast/chemistry; Breast Neoplasms/chemistry; Breast Neoplasms/pathology; Carcinoma, Ductal, Breast/chemistry; Carcinoma, Ductal, Breast/pathology; Cell Membrane/chemistry; Cyclin D1/analysis; Cytoskeletal Proteins/analysis; Female; Follistatin-Related Proteins; Glycoproteins/analysis; Glycoproteins/metabolism; Humans; Immunohistochemistry; In Situ Hybridization; Proto-Oncogene Proteins/analysis; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-myc/analysis; Signal Transduction; Trans-Activators; Wnt Proteins; Wnt1 Protein; Zebrafish Proteins; beta Catenin

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:MYC

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:WNT1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCND1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CTNB1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SFRP4

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:WNT1

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CTNB1

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYC

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SFRP4

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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