ABSTRACT
AIMS AND BACKGROUND: Increasing evidence claims that autophagy is essential for breast cancer progression. Girdin was found highly expressed in breast cancers. It has been reported that Girdin attenuates autophagy in HeLa cells. We explored the relationship between Girdin expression and autophagic patterns in breast cancer. METHODS AND STUDY DESIGN: In the study, Girdin expression and autophagic activity were investigated in a series of 99 invasive ductal breast carcinomas after immunohistochemical staining for the autophagy-associated proteins LC3-II and Girdin. RESULTS: The level of Girdin expression negatively correlated with LC3-II level, which represents autophagic activity (r = -0.289), and positively correlated with lymph node metastasis (r = 0.472). Girdin level was found no different in the "diffuse cytoplasmic" and "stone-like" patterns of LC3-II. CONCLUSIONS: Up-regulated autophagy was negatively associated with Girdin level. There was a significant correlation between Girdin expression and lymph nodes metastasis in invasive ductal breast carcinoma.
Subject(s)
Autophagy , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Microfilament Proteins/metabolism , Microtubule-Associated Proteins/metabolism , Vesicular Transport Proteins/metabolism , Adult , Aged , Breast Neoplasms/pathology , Breast Neoplasms/physiopathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/physiopathology , Female , Humans , Immunohistochemistry , Lymphatic Metastasis , Middle Aged , Neoplasm GradingABSTRACT
Although some evidence has been documented on EGFR/PI3K mediation of Akt activation in breast cancers, ILK and DNA-PK have not been investigated so far. The aim of this study was to analyze the expression of phosphorylated Akt (pAkt) in breast cancer, with respect to its upstream regulators. The immunostaining of pAkt (Ser473) in 70 invasive breast cancers revealed that status of CerbB2 could play a major role in Akt phosphorylation, while ILK was also involved in the stimulated level of pAkt. The results would provide an important clue for the activation of Akt and potential targeted therapy in breast cancer.
Subject(s)
Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Intraductal, Noninfiltrating/metabolism , Gene Expression Regulation, Neoplastic , Proto-Oncogene Proteins c-akt/metabolism , Receptor, ErbB-2/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Intraductal, Noninfiltrating/pathology , DNA-Activated Protein Kinase/metabolism , Female , Humans , Immunohistochemistry , Nuclear Proteins/metabolism , Phosphorylation , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Receptor, ErbB-2/genetics , Retrospective Studies , Signal Transduction/physiologyABSTRACT
Girdin is a downstream effector of epidermal growth factor receptor (EGFR)-AKT and interacts with actin and microtubule. Increasing evidence confirmed that Girdin played an important role in cell migration. Here we report that Girdin also regulates cell division. Overexpression or suppression of Girdin leads to attenuated cell proliferation. Imaging of mitotic cells revealed that Girdin is located in the cell division apparatus such as centrosome and midbody. The sub-cellular localization of Girdin was dependent on the domains, which interacted with actin or microtubules. Overexpression of Girdin lead to increased centrosome splitting and amplification. In addition, data show that pAKT also locates in both the centrosome and midbody, indicating the regulating role of AKT in Girdin-mediated cell division. To elucidate the effect of Girdin on tumor growth in vivo, HeLa cells infected with retrovirus harboring either control or Girdin shRNAs were injected subcutaneously into the immunocompromised nude mice. Downregulation of Girdin by shRNA markedly inhibited the cell growth of subcutaneously transplanted tumors in nude mice. These data demonstrate that Girdin is important for efficient cell division. Taking our previous data into consideration, we speculate that Girdin regulates both cell division and cell migration through cytoskeletal molecules.
