Secreted Frizzled-related Protein 2 (SFRP2) is Highly Expressed in Canine Mammary Gland Tumors but not in Normal Mammary Glands
Resource
Breast Cancer Research and Treatment 84 (2): 139-149
Journal
Breast Cancer Research and Treatment
Journal Volume
84
Journal Issue
2
Pages
139-149
Date Issued
2004
Date
2004
Author(s)
Abstract
Canine mammary gland tumor (MGT) is the commonest tumor in female dogs and a good animal model of human breast cancer. A group of newly identified genes encoding secreted frizzled-related proteins (SFRP) have been implicated in apoptosis regulation and tumorigenesis. Canine mammary tissues from 50 spontaneous MGTs and 10 normal mammary glands (MGs) were obtained from surgically excised specimens and analyzed for expression of SFRP2, β-catenin, and cyclin D1. By RT-PCR and in situ hybridization, SFRP2 gene was found abundantly expressed in neoplastic mammary tissues but not in normal mammary tissues, suggesting that SFRP2 may contribute as a tumor marker in canine MGTs. By immunohistochemical staining, the immunoreactivity of the SFRP2 protein was detected in more diverse areas than SFRP2 mRNA expression, including nuclei or/and cytoplasm and extracellular matrix of the tumor. In tumor masses, β-catenin lost its tight association with the membrane and diffused into the nucleus. The expression of β-catenin (79.4% positive) and cyclin D1 (71.4% positive) was also increased in MGTs. In the course of tumor progression, SFRP2 mRNA (p < 0.05) and β-catenin protein (p < 0.01) steadily increased but not in cyclin D1. The level of SFRP2 was linearly correlated with its downstream target β-catenin (p < 0.05), but not correlated with cyclin D1 (p < 0.5). As revealed in this study, the exclusive overexpression of SFRP2 in canine MGTs suggests that SFRP2 is a potential candidate gene for further investigation of mammary tumorigenesis and complex etiology of the canine model of mammary neoplasms.
Subjects
β-catenin; Cyclin D1; Dog; Mammary gland tumor; Secreted frizzled-related protein 2; SFRP2; Tumor marker; Wnt signaling
SDGs
Other Subjects
beta catenin; cyclin D1; frizzled protein; membrane protein; messenger RNA; secreted frizzled related protein 2; tumor marker; unclassified drug; Wnt1 protein; animal cell; animal experiment; animal model; animal tissue; apoptosis; article; breast tumor; controlled study; dog; extracellular matrix; female; gene; gene identification; gene targeting; immunoreactivity; in situ hybridization; nonhuman; nucleotide sequence; priority journal; protein expression; protein phosphorylation; protein secretion; receptor binding; reverse transcription polymerase chain reaction; SFRP2 gene; signal transduction; Animals; beta Catenin; Cyclin D1; Cytoskeletal Proteins; Disease Models, Animal; Dogs; Female; Gene Expression Regulation, Neoplastic; Immunohistochemistry; In Situ Hybridization; Mammary Glands, Animal; Mammary Neoplasms, Animal; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Trans-Activators; Tumor Markers, Biological
Type
journal article
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