title: Cyclin D3 predicts disease-free survival in breast cancer.
abstract: BACKGROUND
  Cyclin D3, which induces progression through the G1 phase of the cell cycle, is a regulator of Cyclin-dependent kinases 4 and 6. Previous studies revealed that abnormal expression of Cyclin D3 was found in many different cancers. However, the role of Cyclin D3 in breast cancer (BC) remains unknown. The aim of this study is to examine the expression pattern of Cyclin D3 in BC and to evaluate its biological role and clinical significance in prognosis prediction. The mechanism involved is also evaluated.
  
  
  METHODS
  Immunohistochemical staining was used to detect the expression of Cyclin D3. qRT-PCR was used to detect the mRNA level of Cyclin D3 in BC tissues and BC cell lines. Transwell assay was used to examine the role of Cyclin D3 in the migration and invasion of BC cells. Mass Spectrometry was used to search for the interacting protein with Cyclin D3. Co-Immunoprecipitation assay and GST-Pull Down assay were used to validate the interaction of Cyclin D3 and its interaction protein.
  
  
  RESULTS
  Through detecting Cyclin D3 expression in 243 breast cancer patients' tissue array, we found Cyclin D3 expression was correlated with ER status (p = 0.000), PR status (p = 0.001), HER2 status (p = 0.002) and tumor differentiation (p = 0.045). The Kaplan-Meier survival curves indicated that the disease free survival (DFS) was significantly poor in high Cyclin D3 expression BC patients (p = 0.004). Furthermore, expression of Cyclin D3 was significantly associated with BC prognosis and was shown to be an independent prognostic marker in breast cancer (p = 0.028). By IHC staining and qPCR detection, Cyclin D3 expression was found to be down-regulated both in BC tissues and in BC cell lines compared with the corresponding normal controls. Further investigation showed Cyclin D3 was involved in the metastasis of BC cells and physically interacted with actin in vivo and in vitro.
  
  
  CONCLUSIONS
  Our studies revealed that Cyclin D3 was upregulated in breast cancer and represented a novel predictor of BC prognosis.
authors.affiliation: Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Building 7, No. 270 Dong An Road, Shanghai, 200032 China.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Chi
authors.affiliation: Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Building 7, No. 270 Dong An Road, Shanghai, 200032 China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Building 7, No. 270 Dong An Road, Shanghai, 200032 China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Building 7, No. 270 Dong An Road, Shanghai, 200032 China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.
authors.forename: Xuxia
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Building 7, No. 270 Dong An Road, Shanghai, 200032 China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Wu
keywords: Actin; Breast cancer; Cyclin D3; Disease-free survival