Details

Autor(en) / Beteiligte

• Wang, H
• Mannava, S
• Grachtchouk, V
• Zhuang, D
• Soengas, M S
• Gudkov, A V
• Prochownik, E V
• Nikiforov, M A

Titel

c-Myc depletion inhibits proliferation of human tumor cells at various stages of the cell cycle

Ist Teil von

• Oncogene, 2008-03, Vol.27 (13), p.1905-1915

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• A major role for c-Myc in the proliferation of normal cells is attributed to its ability to promote progression through G 1 and into S phase of the cell cycle. The absolute requirement of c-Myc for cell cycle progression in human tumor cells has not been comprehensively addressed. In the present work, we used a lentiviral-based short hairpin RNA (shRNA) expression vector to stably reduce c-Myc expression in a large number of human tumor cell lines and in three different types of normal human cells. In all cases, cell proliferation was severely inhibited, with normal cells ultimately undergoing G 0 /G 1 growth arrest. In contrast, tumor cells demonstrated a much more variable cell cycle response with cells from several lines accumulating in S or G 2 /M phases. Moreover, in some tumor lines, the phase of cell cycle arrest caused by inhibition of c-Myc could be altered by depleting tumor suppressor protein p53 or its transcriptional target p21 CIP/WAF . Our data suggest that, as in the case of normal cells, c-Myc is essential for sustaining proliferation of human tumor cells. However its rate-limiting role in cell cycle control is variable and is reliant upon the status of other cell cycle regulators.