Establishment and characterization of murine small cell lung carcinoma cell lines derived from HPV-16 E6/E7 transgenic mice

Laura Carraresi, Rosanna Martinelli, Alessandro Vannoni, Massimo Riccio, Maja Dembic, Sergio Tripodi, Marcella Cintorino, Spartaco Santi, Elisa Bigliardi, Mario Carmellini, Mara Rossini

Research output: Contribution to journalArticlepeer-review

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 μm 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.

Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalCancer Letters
Volume231
Issue number1
DOIs
Publication statusPublished - Jan 8 2006

Keywords

  • Achaete-scute homologue 1
  • Caveolin-1
  • Chromogranin A
  • Confocal immunofluorescence
  • HPV-16 E6/E7 transgenic mice
  • Microtubule-associated protein 2
  • Murine cell lines
  • Secretogranin 2
  • SEM
  • Small cell lung carcinoma
  • TEM

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

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