Elevated Ki-67 expression is correlated with TNFalpha- and IFNgamma-induced apoptosis in tumour cells.
The expression of Ki-67 in tumour cells induced to apoptosis by tumour-necrosis-factor alpha (TNFalpha) and interferon gamma (IFNgamma) was studied. Ki-67 is known as a proliferation marker which is expressed in cycling cells, but not in resting quiescent or Go cells. In numerous studies, the proportion of tumours expressing Ki-67 was determined and related to tumour grade or prognosis. A high percentage of Ki-67 expressing cells and a low apoptotic index were regarded as an indication of a progressive tumour. This implied that Ki-67 expression and apoptosis were contrary traits. In this study, the level of Ki-67 expression in human tumour cells in culture was measured after induction of apoptosis. The Ki-67 level was determined by flow cytometry and apoptosis was measured by various methods including PARP degradation (western blot) in detached and floating cells. While the floating cells were all apoptotic, more than 80% of the attached cells showed no apoptotic signs. The Ki-67 level of apoptotic cells was elevated about 3-fold compared to viable attached control cells. However, the cytokine-treated attached cells also expressed Ki-67 at similar high levels to the apoptotic floating cells, depending on sensitivity. The plot of Ki-67 level vs. remaining cells after treatment revealed a strong correlation between the level of Ki-67 expression and the sensitivity to cytokine-induced apoptosis. This implies that proliferation pathways and apoptotic signal transduction are connected.
Baisch
Heinz
H
Institute of Biophysics and Radiobiology, University-Hospital Hamburg-Eppendorf, Germany. baisch@uke.uni-hamburg.de
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011065:Poly(ADP-ribose) Polymerases