title: Deregulated LAP2α expression in cervical cancer associates with aberrant E2F and p53 activities.
abstract: Lamina-associated polypeptide 2 alpha (LAP2α) plays a role in maintaining nuclear structure, in nuclear assembly/disassembly, and in transcriptional regulation. Elevated LAP2α mRNA expression has been previously reported to associate with certain cancer types. The aim of this study was to investigate LAP2α expression in cervical cancer and transformed cells and to identify factors that associate with its differential expression. LAP2α expression was found to be elevated in cervical cancer tissue by microarray, qRT-PCR, and immunofluorescence analyses. LAP2α also showed elevated expression in cervical cancer cell lines and in transformed fibroblasts compared with normal cells. To determine factors associated with elevated LAP2α in cervical cancer, the effect of inhibiting HPV E7 and E6 oncoproteins was investigated. E7 inhibition resulted in a decrease in phosphorylated Rb and an associated decrease in LAP2α, suggesting a role for E2F in regulating LAP2α expression. This finding was confirmed by inhibiting DP1, a co-activator of E2F, which resulted in decreased LAP2α levels. Inhibition of E6 resulted in elevated p53 and an associated decrease in LAP2α, suggesting that p53 associates with the negative regulation of LAP2α expression. This hypothesis was tested by inhibiting p53 in normal cells, and a resultant increase in LAP2α expression was observed. In conclusion, this study provides evidence for elevated LAP2α expression in cervical cancer and suggests that E2F and p53 activities associate with the positive and negative regulation of LAP2α expression, respectively.
authors: Faculty of Health Sciences, Division of Medical Biochemistry, University of Cape Town, Institute of Infectious Disease and Molecular Medicine, South Africa.
authors: Michelle C
authors: MC
authors: Ward
authors: Pauline J
authors: PJ
authors: van der Watt
authors: Gannie
authors: G
authors: Tzoneva
authors: Virna D
authors: VD
authors: Leaner
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D016160:Retinoblastoma Protein / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C093413:lamina-associated polypeptide 2