Effects of c-MYC oncogene modulation on differentiation of human small cell lung carcinoma cell lines

Academic Article

Abstract

  • Amplification and over-expression of oncogenes of the myc family are related to the prognosis of certain solid tumors such as small cell lung cancer (SCLC). For SCLC, c-myc is the oncogene most consistently found to correlate with the end stage behaviour of the tumour, in particular with survival after chemotherapeutic treatment. C-myc is important in many cellular processes such as proliferation, differentiation and apoptosis. In the present study the relationship between c-myc and differentiation was analyzed by down-regulation of endogenous c-myc protein, using two approaches: first by coculturing with antisense (AS) oligodeoxynucleotides (ODN) in the human SCLC cell line GLC and its 6-fold cisplatin resistant subline GLC -CDDP, second by stable transfection of GLC -CDDP with a dexamethasone-inducible AS c-myc expression vector. Basic characterization of the differentiation status of GLC and GLC -CDDP showed a decrease in neuroendocrine differentiation in GLC -CDDP compared to GLC . Cytokeratin was absent in both cell lines. No significant differences in expression of adhesion molecules or myeloid antigens were observed between the lines. Vimentin expression was higher in GLC -CDDP compared to GLC .(AS c-myc ODN)-induced growth inhibition and down-regulation of endogenous c-myc protein further decreased neuroendocrine differentiation (CD57 positive cells) in GLC -CDDP without affecting the expression of other antigens such as vimentin (intermediate filament), CD15 myeloid antigen) and VLA-α4 (adhesion molecule) and did not alter the expression of these antigens in GLC . (AS c-myc RNA)-induced growth inhibition did not significantly afffect the expression of the tested antigens in the AS c-myc transfected GLC -CDDP/AS cell line. No effect of nonsense c-myc ODN or dexamethasone-induced control RNA (controls) was observed. 4 4 4 4 4 4 4 4 4 4 4 4
  • Author List

  • Van Waardenburg RCAM; Meijer C; Pinto-Sietsma SJ; De Vries EGE; Timens W; Mulder NM
  • Start Page

  • 91
  • End Page

  • 95
  • Volume

  • 18
  • Issue

  • 1 A