ABSTRACT
No abstract available.
Subject(s)
Anaphase-Promoting Complex-Cyclosome , Neoplasms , Cell Nucleus , Colorectal Neoplasms , Anaplasia , AneuploidyABSTRACT
PURPOSE: The anaphase-promoting complex (APC) is a multiprotein complex with E3 ubiquitin ligase activity and is required for ubiquitination of securin and cyclin-B. Several APC-targeting molecules are reported to be oncogenes. Dysregulation of APC may be associated with tumorigenesis. This study examines the relationship between APC expression and clinicopathological factors and evaluates the possibility of an aberrant APC function in colorectal carcinomas (CRCs). METHODS: To determine whether the loss of APC7 expression is related to tumorigenesis, we used tissue micro-arrays in 114 resected CRCs to scrutinize the expressions of APC7 and Ki-67 immunohistochemistry and to find relations with clinocopathologic parameters. The expression of APC7 was defined as positive for summed scores of staining intensities from 0 to 3+. RESULTS: Forty-four cases (67.7%) of colon cancer and 38 cases (77.6%) of rectal cancer showed immunopositive reactions to APC. The grade of APC expression was not statistically correlated with tumor location, age, T or TNM stage, or differentiation. However, the expression of APC did correlate with the expression of Ki-67 and to the tumor recurrent. Higher APC expression showed the better 5-year overall survival rate in 74% of grades 2, 3 groups (high expression) than 57% of grades 0, 1 groups (lower expression) respectively (P = 0.042). CONCLUSION: Positive APC expression may be a good prognostic factor for patients with CRC, and the loss of APC expression in tumor tissue may be related with the risk for recurrence and a poor survival rate compared to high APC expression. Further study of APC in controlling the cell cycle as aberrant function in CRC is needed.
Subject(s)
Humans , Adenocarcinoma , Anaphase-Promoting Complex-Cyclosome , Carcinogenesis , Cell Cycle , Colonic Neoplasms , Colorectal Neoplasms , Immunohistochemistry , Oncogenes , Rectal Neoplasms , Recurrence , Securin , Survival Rate , Ubiquitin , Ubiquitin-Protein Ligases , UbiquitinationABSTRACT
A recently identified protein, FAN1 (FANCD2-associated nuclease 1, previously known as KIAA1018), is a novel nuclease associated with monoubiquitinated FANCD2 that is required for cellular resistance against DNA interstrand crosslinking (ICL) agents. The mechanisms of FAN1 regulation have not yet been explored. Here, we provide evidence that FAN1 is degraded during mitotic exit, suggesting that FAN1 may be a mitotic substrate of the anaphase-promoting cyclosome complex (APC/C). Indeed, Cdh1, but not Cdc20, was capable of regulating the protein level of FAN1 through the KEN box and the D-box. Moreover, the up- and down-regulation of FAN1 affected the progression to mitotic exit. Collectively, these data suggest that FAN1 may be a new mitotic substrate of APC/CCdh1 that plays a key role during mitotic exit.
Subject(s)
Humans , Anaphase-Promoting Complex-Cyclosome , Bone Neoplasms , Metabolism , Pathology , Cadherins , Genetics , Metabolism , Cdc20 Proteins , Cell Cycle Proteins , Genetics , Metabolism , Cell Line, Tumor , Exodeoxyribonucleases , Genetics , Metabolism , HEK293 Cells , Mitosis , Osteosarcoma , Metabolism , Pathology , Ubiquitin-Protein Ligase Complexes , Genetics , MetabolismABSTRACT
CUE domain-containing 2 (CUEDC2) is a protein involved in the regulation of the cell cycle, inflammation, and tumorigenesis and is highly expressed in many types of tumors. CUEDC2 is phosphorylated by Cdk1 during mitosis and promotes the release of anaphase-promoting complex or cyclosome (APC/C) from checkpoint inhibition. CUEDC2 is also known to interact with IkB kinase α (IKKα) and IKKβ and has an inhibitory role in the activation of transcription factor nuclear factor-κB. Moreover, CUEDC2 plays an important role in downregulating the expression of hormone receptors estrogen receptor-α and progesterone receptor, thereby impairing the responsiveness of breast cancer to endocrine therapies. In this review, current knowledge on the multi-functions of CUEDC2 in normal processes and tumorigenesis are discussed and summarized.
Subject(s)
Female , Humans , Anaphase-Promoting Complex-Cyclosome , Breast Neoplasms , Pathology , Carrier Proteins , Metabolism , Cell Cycle Proteins , Metabolism , Cell Transformation, Neoplastic , Pathology , Estrogen Receptor alpha , Metabolism , I-kappa B Kinase , Metabolism , Inflammation , Pathology , M Phase Cell Cycle Checkpoints , Membrane Proteins , Metabolism , Mitosis , NF-kappa B p50 Subunit , Metabolism , Receptor-Interacting Protein Serine-Threonine Kinases , Metabolism , Signal Transduction , Ubiquitin-Protein Ligase Complexes , Metabolism , UbiquitinationABSTRACT
BACKGROUND: The anaphase promoting complex (APC) promotes the degradation of mitotic cyclins as well as other substrates involved in sister chromatid adhesion. This study was carried out to examine the relationship between the APC expression and the clinicopathological variables, in an attempt to determine the role of the APC in the proliferation of lung cancer and to evaluate the possibility of an aberrant APC function in surgically resected squamous cell carcinomas and adenocarcinomas of the lung. METHODS: Immunohistochemical staining was performed for APC, Ki-67, cyclin B1, Cdc2, MMP-2 and VEGF in 55 cases of squamous cell carcinoma and 34 cases of adenocarcinoma of the lung, using the avidin-biotin-peroxidase method. RESULTS: The immunohistochemical stains for APC revealed a positive reaction in 49 cases (55.1%). The APC expression level was higher in the cyclin B1-positive group (p= 0.01), the Cdc2-positive group (p=0.001), the MMP-2-positive group (p=0.03), the group with lymph node metastasis (61.4% vs 48.9%), and the group with stage II/III cancer (60.7%) compared with those with stage I (42.9%). CONCLUSIONS: The APC may have an aberrant function, such as a change in its role in controlling the cell cycle, and might be associated with the invasiveness and proliferation of tumor cells.
Subject(s)
Humans , Adenocarcinoma , Anaphase , Anaphase-Promoting Complex-Cyclosome , Carcinoma, Squamous Cell , Cell Cycle , Chromatids , Coloring Agents , Cyclin B1 , Cyclins , Lung Neoplasms , Lung , Lymph Nodes , Neoplasm Metastasis , Siblings , Vascular Endothelial Growth Factor AABSTRACT
BACKGROUND: Oncogene expression in Paget's disease of the breast is not well known. To characterize invasive ductal carcinoma associated with Paget's disease, we studied expression of anaphase promoting complex (APC) with its regulatory proteins. METHODS: Immunohistochemical stainings were done with 10 cases of invasive ductal carcinoma associated with Paget's disease for APC, pituitary tumor transforming gene (PTTG), cyclin B1, p53, cyclin D1, and c-erbB-2. The expressions of these markers in Paget's disease were compared with those in the associated with carcinoma. RESULTS: APC, PTTG, cyclin B1, and c-erbB-2 were positive in all of the cases with both Paget's disease and underlying carcinoma. p53 was expressed in Paget's disease of 6 cases (60%) and in carcinoma of 7 cases (70%). Cyclin D1 was positive in Paget's disease of 8 cases (80%) and in carcinoma of 9 cases (90%). CONCLUSIONS: Breast carcinomas with Paget's disease seem to be distinguished by the high expression of APC, cyclin B1, PTTG, c-erbB2, and cyclin D1 in contrast to breast cancers without Paget's disease. Furthermore, the similar expression patterns of APC and APC regulatory proteins in both Paget's disease and underlying breast cancer support the epidermotropic theory as its pathogenetic mechanism.