Authors: Kelly K. Haagenson, Larry Tait, Juan Wang, Malathy P. Shekhar, Lisa Polin, Wei Chen and Gen Sheng Wu

Kelly K. Haagenson

Karmanos Cancer Institute; Detroit, MI USA; Department of Oncology; Wayne State University School of Medicine; Detroit, MI USA; Graduate Program in Cancer Biology; Wayne State University School of Medicine; Detroit, MI USA

Larry Tait

Karmanos Cancer Institute; Detroit, MI USA

Juan Wang

Karmanos Cancer Institute; Detroit, MI USA

Malathy P. Shekhar

Karmanos Cancer Institute; Detroit, MI USA; Department of Oncology; Wayne State University School of Medicine; Detroit, MI USA; Department of Pathology; Wayne State University School of Medicine; Detroit, MI USA; Graduate Program in Cancer Biology; Wayne State University School of Medicine; Detroit, MI USA

Lisa Polin

Karmanos Cancer Institute; Detroit, MI USA

Wei Chen

Karmanos Cancer Institute; Detroit, MI USA; Department of Oncology; Wayne State University School of Medicine; Detroit, MI USA

Gen Sheng Wu

Corresponding author: wug@karmanos.org
Karmanos Cancer Institute; Detroit, MI USA; Department of Oncology; Wayne State University School of Medicine; Detroit, MI USA; Department of Pathology; Wayne State University School of Medicine; Detroit, MI USA; Graduate Program in Cancer Biology; Wayne State University School of Medicine; Detroit, MI USA

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.

Received: April 29, 2012; Accepted: June 6, 2012; Published Online: July 24, 2012

Preview: