title: Gankyrin is frequently overexpressed in breast cancer and is associated with ErbB2 expression.
abstract: Gankyrin is a subunit of the 26S proteasome, and has been known to degrade p53 and retinoblastoma protein and promote the tumorigenicity and metastasis in some malignancies. However, the role of gankyrin in breast cancer has not been explored. In this study, we investigated the expression of gankyrin in breast cancer and evaluated its effect on breast cancer. Representative cancer tissues including normal breasts from 60 patients with breast cancer were stained immunohistochemically for gankyrin, estrogen receptor, progesterone receptor, and ErbB2. We evaluated the relationship between gankyrin expression and clinicopathologic parameters or prognostic markers. We also attempted to clarify the mechanism of gankyrin involved in breast carcinogenesis by using MCF7 breast cancer cells. Gankyrin was weakly expressed in normal breast epithelial cells, however, tumor regions of 37/60 (61.7%) cases showed an overexpression of gankyrin. Gankyrin overexpression was associated with extensive intraductal carcinoma (p=0.014) and ErbB2 positivity (p=0.031) in invasive ductal carcinoma. In MCF7 breast cancer cells, downregulation of gankyrin was associated with a reduction of cell proliferation and tumorigenicity. In conclusion, gankyrin was identified in normal breasts and overexpressed in invasive breast cancers. The overexpression of gankyrin was associated with extensive intraductal carcinoma and ErbB2 expression in breast cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Brain Korea 21 Division of Cell Transformation and Restoration, Ajou University, School of Medicine, Suwon 443-721, Republic of Korea.
authors.forename: Yeong Hwa
authors.initials: YH
authors.lastname: Kim
authors.forename: Jang-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Yong Won
authors.initials: YW
authors.lastname: Choi
authors.forename: Seo Kyung
authors.initials: SK
authors.lastname: Lim
authors.forename: Hyunee
authors.initials: H
authors.lastname: Yim
authors.forename: Seok Yun
authors.initials: SY
authors.lastname: Kang
authors.forename: Yong Sik
authors.initials: YS
authors.lastname: Chung
authors.forename: Ga-Young
authors.initials: GY
authors.lastname: Lee
authors.forename: Tae Jun
authors.initials: TJ
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D046988:Proteasome Endopeptidase Complex; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C403591:PSMD10 protein, human; C508053:ERBB2 protein, human