title: CDC23 regulates cancer cell phenotype and is overexpressed in papillary thyroid cancer.
abstract: Cancer gender disparities have been observed for a variety of human malignancies. Thyroid cancer is one such example where there is a dramatic difference in the incidence, aggressiveness, and death rate by gender. The molecular basis for gender disparity is poorly understood. To address this, we performed genome-wide gene expression profiling in matched papillary thyroid cancer (PTC) samples and identified nine candidate genes differentially expressed by gender. One of these genes was CDC23 that was upregulated in PTC in men compared with women. Because the function and expression of CDC23 is unknown in eukaryotic cells, we further characterized the expression of CDC23 in normal, hyperplastic, and PTC tissue samples. We found CDC23 was overexpressed in PTC and absent in normal and hyperplastic thyroid tissue. In thyroid cancer cells, functional knockdown of CDC23 resulted in an increase in the number of cells in both the S and G(2)M phases of the cell cycle, and an inhibition of cellular proliferation, tumor spheroid formation, and anchorage-independent growth. Cellular arrest in both S and G(2)M phases was associated with significant cyclin B1 and securin protein accumulation after CDC23 knockdown. Moreover, the effect of CDC23 on cellular proliferation and cell cycle progression was reversed on triple knockdown studies of CDC23, cyclin B1, and securin. Our data taken together suggests CDC23 has important biologic effects on cell proliferation and cell cycle progression. The effect of CDC23 on cellular proliferation and cell cycle progression is mediated, at least in part, by cyclin B1 and securin protein levels. Therefore, we propose that CDC23 is a critical regulator of cell cycle and cell growth, and may be involved in thyroid cancer initiation and progression, and may explain the different tumor biology observed by gender.
authors: Endocrine Oncology Section, Surgery Branch, National Cancer Institute, NIH, HHS, Clinical Research Center, Building 10-CRC, Room 3-3940, 10 Center Drive, MSC 1201, Bethesda, Maryland 20892, USA.
authors: Lisa
authors: L
authors: Zhang
authors: Reza
authors: R
authors: Rahbari
authors: Mei
authors: M
authors: He
authors: Electron
authors: E
authors: Kebebew
mesh_terms: D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; D002291:Carcinoma, Papillary / Q000235:genetics / Q000276:immunology*; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000235:genetics / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064249:Securin; D012737:Sex Factors; D013964:Thyroid Neoplasms / Q000235:genetics / Q000276:immunology*
chemical_list: D064196:Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome; C577440:CDC23 protein, human; D018797:Cell Cycle Proteins; D056744:Cyclin B1; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human