Reduced expression of ubiquitin ligase FBXW7 mRNA is associated with poor prognosis in breast cancer patients.

Abstract

FBXW7 is a cell cycle regulatory gene that ubiquitinates positive cell cycle regulators such as c-Myc and cyclin E, allowing for cell cycle exit. Defects in the FBXW7 gene that lead to cell cycle re-entry and expedite the G1-S transition is thought to be one of the causes of cancer development. However, its clinical importance for breast cancer patients remains undetermined. This prompted us to investigate its expression level in breast cancer patients to establish its clinical significance. The expression level of FBXW7 mRNA was assessed in 186 cases of primary invasive breast cancer. Correlations between FBXW7 mRNA expression and clinicopathological factors, prognoses and immunohistochemical expression levels of Ki-67, FBXW7, c-Myc and cyclin E were analyzed. In vitro investigation of FBXW7 gene silencing in a breast cancer cell line was conducted. FBXW7 mRNA was expressed at significantly lower levels in patients with high histological grade and hormone receptor-negative tumors. Patients with lower FBXW7 mRNA expression had a poorer prognosis for breast cancer-specific survival than those with higher expression. A high Ki-67 labeling index and positive cyclin E protein expression were significantly correlated with lower FBXW7 mRNA expression. In vitro, silencing FBXW7 enhanced expression of c-Myc and cyclin E proteins and upregulated both cell proliferation and G1-S transition. In breast cancer, reduced FBXW7 mRNA expression may have independent prognostic potential through the enhanced function of cell cycle regulatory proteins.

• Authors: Mutsuko Ibusuki, Yutaka Yamamoto, Satoru Shinriki, Yukio Ando, Hirotaka Iwase
• Journal: Cancer science (Cancer Sci) Vol. 102 Issue 2 Pg. 439-45 (Feb 2011) ISSN: 1349-7006 [Electronic] England
• PMID: 21134077 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 Japanese Cancer Association.

Chemical References

• Biomarkers, Tumor
• Cell Cycle Proteins
• F-Box Proteins
• F-Box-WD Repeat-Containing Protein 7
• FBXW7 protein, human
• RNA, Messenger
• Ubiquitin-Protein Ligases

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (analysis, genetics)
• Blotting, Western
• Breast Neoplasms (enzymology, genetics, pathology)
• Cell Cycle Proteins (biosynthesis, genetics)
• Cell Separation
• F-Box Proteins (biosynthesis, genetics)
• F-Box-WD Repeat-Containing Protein 7
• Female
• Flow Cytometry
• Gene Expression
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Middle Aged
• Neoplasm Staging
• Prognosis
• RNA, Messenger (analysis)
• Ubiquitin-Protein Ligases (biosynthesis, genetics)