title: Cullin-3 protein expression levels correlate with breast cancer progression.
abstract: Cullin-3 is a component of the Cullin-Ring ubiquitin ligase (CRL) family that plays an important role in mediating protein degradation. Deregulation of Cullin-3 expression has been observed in human cancers; however, a role for Cullin-3 in tumor progression has not been previously recognized. Using the MCF10DCIS.com human breast cancer xenograft model, we show that Cullin-3 is increasingly expressed during progression from comedo ductal carcinoma in situ (DCIS) to invasive carcinomas. Cullin-3 protein is not detected in early lesions but is noticeably increased in DCIS tumors and significantly overexpressed in invasive cancers. In experimental metastasis assays, high expression of Cullin-3 was observed in the lung site. Importantly, Cullin-3 staining is detected in human breast cancer tissues, not in normal breast tissues and its expression level positively correlates with tumor stage. These data suggest that Cullin-3 may play an important role in tumor progression from DCIS to invasive cancer and may serve as a biomarker for the diagnosis of aggressive breast cancer.
authors: Karmanos Cancer Institute, Detroit, MI ,USA.
authors: Kelly K
authors: KK
authors: Haagenson
authors: Larry
authors: L
authors: Tait
authors: Juan
authors: J
authors: Wang
authors: Malathy P
authors: MP
authors: Shekhar
authors: Lisa
authors: L
authors: Polin
authors: Wei
authors: W
authors: Chen
authors: Gen Sheng
authors: GS
authors: Wu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D044842:Cullin Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging; D011379:Prognosis; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; C503645:CUL3 protein, human; D044842:Cullin Proteins