Establishment and characterization of murine small cell lung carcinoma cell lines derived from HPV-16 E6/E7 transgenic mice.
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.
Carraresi
Laura
L
Department of Physiopathology and Experimental Medicine, University of Siena, Via Aldo Moro, 53100 Siena, Italy.
Martinelli
Rosanna
R
Vannoni
Alessandro
A
Riccio
Massimo
M
Dembic
Maja
M
Tripodi
Sergio
S
Cintorino
Marcella
M
Santi
Spartaco
S
Bigliardi
Elisa
E
Carmellini
Mario
M
Rossini
Mara
M
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
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