Secreted frizzled-related protein 2 (SFRP2) is highly expressed in canine mammary gland tumors but not in normal mammary glands.
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, beta-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, beta-catenin lost its tight association with the membrane and diffused into the nucleus. The expression of beta-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 beta-catenin protein ( p < 0.01) steadily increased but not in cyclin D1. The level of SFRP2 was linearly correlated with its downstream target beta-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.
Lee
Jia-Lin
JL
Department and Graduate Institute of Veterinary Medicine, College of Bio-Resources and Agriculture, National Taiwan University, Taiwan, ROC.
Chang
Ching-Jin
CJ
Wu
Szu-Ying
SY
Sargan
David R
DR
Lin
Chung-Tien
CT
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008321:Mammary Glands, Animal / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D011506:Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1