Article

Resistance to apoptosis of HPV 16-infected laryngeal cancer cells is associated with decreased Bak and increased Bcl-2 expression.

Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Sir Y.K. Pao Center for Cancer, Shatin, N.T., Hong Kong, China.
Cancer Letters (impact factor: 4.24). 04/2004; 205(1):81-8. DOI:10.1016/j.canlet.2003.09.035 pp.81-8
Source: PubMed

ABSTRACT Human papillomavirus type 16 (HPV 16) plays an etiological role in human laryngeal carcinoma. Apoptosis is closely associated with various biological processes including oncogenesis. This study investigated how HPV 16 oncoproteins E6 and E7 affect apoptosis in human laryngeal cancer cells. We established two human laryngeal cancer cell lines that expressed HPV 16 E6 and E7, respectively. Using these two cell lines, we found that both E6 and E7 exhibited an inhibitive effect on apoptosis induced by tumor necrosis factor alpha and cycloheximide. In both transfected cell lines, the expression of pro-apoptotic Bak was reduced and that of anti-apoptotic Bcl-2 was over-expressed. However, the expression of caspase-3 and caspase-8 was not significantly different between the E6- and E7-transfected cells and the control cells without HPV 16. p53 Protein was not detected in either the transfected or the non-transfected cells. Our study indicates that: (1) HPV 16 E6 and E7 oncoproteins are capable of inhibiting apoptosis in laryngeal squamous carcinoma cells; (2) the mechanism modulated by E6 and E7 involves the over-expression of Bcl-2 and the down-regulation of Bak; (3) the anti-apoptotic pathway is not related to the level of p53, caspase-3, or caspase-8. These results suggest that the dysregulation of apoptotic molecules Bak and Bcl-2 by HPV 16 E6 and E7 plays a role in the prolongation of cell survival, which may subsequently contribute to the development of human laryngeal cancer.

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    Article: Accumulation of the pro-apoptotic factor Bak is controlled by antagonist factor Mcl-1 availability.
    E Minet, J-P Cosse, C Demazy, M Raes, C Michiels
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    ABSTRACT: Apoptosis has become recognized as a crucial mechanism involved in a wide range of physiological and pathological processes. Following an initial pro-apoptotic signal, controlling phases allow the cell to reinforce or downgrade signals leading to the irrevocable entry into apoptosis. Bak (Bcl-2-antagonist killer) is a mitochondrial pore-forming pro-apoptotic effector inhibited through titration by the anti-apoptotic protein Mcl-1 (Myeloid cell leukemia-1). Viruses have taken advantage of proteasome-dependent degradation of Bak as a mechanism to prevent apoptosis in infected cells. It is not clear however whether regulation of Bak protein level is involved in other physiological processes. In this report, we show that Mcl-1 level is paralleled by Bak while a Mcl-1 non-interacting mutant of Bak does not accumulate in cells. This mechanism is proteasome independent. Following serum withdrawal, Bak accumulation becomes independent of Mcl-1 level and cells are sensitized to pro-apoptotic stimuli. Based on these results, we propose that regulation of Mcl-1-Bak steochiometry is a control mechanism used as a checkpoint to prevent or allow entry into apoptosis.
    APOPTOSIS 07/2006; 11(6):1039-47. · 4.79 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

anti-apoptotic Bcl-2
 
apoptotic molecules Bak
 
control cells
 
E7 oncoproteins
 
E7-transfected cells
 
etiological role
 
expressed HPV 16 E6
 
HPV 16 oncoproteins E6
 
human laryngeal cancer
 
human laryngeal cancer cell lines
 
human laryngeal cancer cells
 
human laryngeal carcinoma
 
Human papillomavirus type 16
 
inhibiting apoptosis
 
laryngeal squamous carcinoma cells
 
pro-apoptotic Bak
 
transfected cell lines
 
tumor necrosis factor alpha
 
two cell lines
 
various biological processes