title: NAV3 copy number changes and target genes in basal and squamous cell cancers.
abstract: The neuron navigator 3 (NAV3) gene on chromosome 12q21 encodes a microtubule plus end tracking protein and belongs to the navigator family of cytoskeletal regulators. Loss of heterozygosity on 12q has previously been suggested to be associated with poor prognosis in cancers of epithelial origin. In this study, we characterized copy number changes of NAV3 in 24 basal cell cancers (BCCs), eight squamous cell cancers (SCCs) and eight non-malignant inflammatory skin lesions by fluorescent in situ hybridization. To identify genes affected by NAV3, we used oligo siRNA gene silencing and gene microarrays to analyse gene expression profiles at several time points post-transfection in primary human keratinocytes. We found NAV3 copy number loss and decreased protein expression in 21% of the BCCs and 25% of the SCCs. In the nodular/superficial BCC subgroup, low-level NAV3 amplification was also observed. NAV3 aberrations were independent of the known chromosome 6 amplifications in BCC. Chromosome 12 polysomy was detected in 33% and 25% of the invasive type of BCC and SCC, respectively. Silencing of NAV3 in primary human keratinocytes revealed 22 differentially expressed genes, mostly related to inflammation. The most relevant of these were validated with qPCR or immunohistochemistry. This pilot study suggests that NAV3 is a novel cancer-associated gene that contributes to the pathogenesis of a subgroup of BCC and SCC.
authors: Department of Dermatology and Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Pilvi
authors: P
authors: Maliniemi
authors: Emilia
authors: E
authors: Carlsson
authors: Anna
authors: A
authors: Kaukola
authors: Kristian
authors: K
authors: Ovaska
authors: Kirsi
authors: K
authors: Niiranen
authors: Olli
authors: O
authors: Saksela
authors: Leila
authors: L
authors: Jeskanen
authors: Sampsa
authors: S
authors: Hautaniemi
authors: Annamari
authors: A
authors: Ranki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C464453:NAV3 protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering