title: Establishment and characterization of murine small cell lung carcinoma cell lines derived from HPV-16 E6/E7 transgenic mice.
abstract: We have established two murine cell lines derived from Small Cell Lung Carcinomas (SCLCs) developed by HPV-E6/E7 transgenic mice. These cells named PPAP-9 and PPAP-10 were isolated from mice bearing tumors, 9 and 10 months old, respectively. The cells, 5 microm in diameter, express HPV oncoproteins and sustain tumor formation after subcutaneous injection in syngenic mice. A detailed analysis indicated the epithelial origin and the neuroendocrine differentiation of these cells. We showed by confocal immunofluorescence the expression of the epithelial marker cytokeratin 5, whose gene promoter was used to direct the expression of HPV E6/E. Cells express several neuroendocrine markers such as CGRP, MAP-2, Ash1, CgrA, Scg2. The neuroendocrine differentiation of these cells was further confirmed by electron microscopy demonstrating neuropeptides secreting granules in their cytoplasm. Furthermore, in agreement with the altered expression observed in the majority of human SCLC we showed in these cells the absence of both p53 and pRB and a dramatic reduction in the expression of Caveolin-1.
authors.affiliation: Department of Physiopathology and Experimental Medicine, University of Siena, Via Aldo Moro, 53100 Siena, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Carraresi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Martinelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vannoni
authors.forename: Massimo
authors.initials: M
authors.lastname: Riccio
authors.forename: Maja
authors.initials: M
authors.lastname: Dembic
authors.forename: Sergio
authors.initials: S
authors.lastname: Tripodi
authors.forename: Marcella
authors.initials: M
authors.lastname: Cintorino
authors.forename: Spartaco
authors.initials: S
authors.lastname: Santi
authors.forename: Elisa
authors.initials: E
authors.lastname: Bigliardi
authors.forename: Mario
authors.initials: M
authors.lastname: Carmellini
authors.forename: Mara
authors.initials: M
authors.lastname: Rossini
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D018288:Carcinoma, Small Cell / Q000473:pathology* / Q000662:veterinary; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000662:veterinary; D051379:Mice; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins