title: KIAA0101 is overexpressed, and promotes growth and invasion in adrenal cancer.
abstract: BACKGROUND
  KIAA0101 is a proliferating cell nuclear antigen-associated factor that is overexpressed in some human malignancies. Adrenocortical neoplasm is one of the most common human neoplasms for which the molecular causes are poorly understood. Moreover, it is difficult to distinguish between localized benign and malignant adrenocortical tumors. For these reasons, we studied the expression, function and possible mechanism of dysregulation of KIAA0101 in human adrenocortical neoplasm.
  
  
  RESULTS
  KIAA0101 mRNA and protein expression levels were determined in 112 adrenocortical tissue samples (21 normal adrenal cortex, 80 benign adrenocortical tumors, and 11 adrenocortical carcinoma (ACC). SiRNA knockdown was used to determine the functional role of KIAA0101 on cell proliferation, cell cycle, apoptosis, soft agar anchorage independent growth and invasion in the ACC cell line, NCI-H295R. In addition, we explored the mechanism of KIAA0101 dysregulation by examining the mutational status. KIAA0101 mRNA (9.7 fold) and protein expression were significantly higher in ACC (p<0.0001). KIAA0101 had sparse protein expression in only a few normal adrenal cortex samples, which was confined to adrenocortical progenitor cells. KIAA0101 expression levels were 84% accurate for distinguishing between ACC and normal and benign adrenocortical tumor samples. Knockdown of KIAA0101 gene expression significantly decreased anchorage independent growth by 80% and invasion by 60% (p = 0.001; p = 0.006). We found no mutations in KIAA0101 in ACC.
  
  
  CONCLUSIONS
  KIAA0101 is overexpressed in ACC. Our data supports that KIAA0101 is a marker of cellular proliferation, promotes growth and invasion, and is a good diagnostic marker for distinguishing benign from malignant adrenocortical neoplasm.
authors.affiliation: Endocrine Oncology Section, Surgery Branch, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Meenu
authors.initials: M
authors.lastname: Jain
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhang
authors.forename: Erin E
authors.initials: EE
authors.lastname: Patterson
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D012333:RNA, Messenger
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C425208:PCLAF protein, human; D012333:RNA, Messenger
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