Association between the expression of E1A oncogene and increased sensitivity to growth inhibition induced by sustained levels of cAMP in rat thyroid cells

Giovanni Villone, Gabriella De Vita, Paolo Chieffi, Antonietta Picascia, Rosita Stanzione, Massimo Santoro, Alfredo Fusco, Donatella Tramontano

Research output: Contribution to journalArticle

Abstract

Objective: The aim of this study was to investigate: (i) whether a persistent increase of cAMP interferes with the proliferation of transformed thyroid cells, and (ii) whether the degree of malignancy is correlated with the sensitivity to a transient and/or sustained increase in intracellular cAMP levels. Design and methods: To address these questions we used thyroid cell lines transformed with E1A oncogene from adenoviruses 5 (PC E1A cell line) or 2 (PC HE4 cell line), or infected with the polyoma murine leukemia virus (PC PyMLV cell line) carrying the middle T gene of the polyoma virus, or, finally, expressing both E1A and PyMLV. These cell lines present various degrees of malignancy: PC E1A and PC HE4 cells are not tumorigenic; PC PyMLV cells induce non-invasive tumors after a long latency period; and PC E1A + PyMLV cells are highly tumorigenic. Results and conclusions: Thyroid cell proliferation required the transient increase of intracellular cAMP levels, while persistent elevation of CAMP blocked the proliferation of normal thyroid PC Cl 3 cells and of PC Cl 3 cells transformed by a variety of different oncogenes. In addition, sustained levels of cAMP induced apoptosis in cells carrying the adenovirus E1A oncogene, but not in cells transformed with other oncogenes or in the wild-type PC Cl 3 cells. Furthermore, middle T gene of the polyoma virus seemed to afford protection only from apoptosis induced by cAMP when middle T is present in thyroid cells along with the E1A gene.

Original languageEnglish
Pages (from-to)286-293
Number of pages8
JournalEuropean Journal of Endocrinology
Volume142
Issue number3
Publication statusPublished - Mar 2000

ASJC Scopus subject areas

  • Endocrinology

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