Nearly 15 types of programmed cell death (PCD) have been identified to date. Among them, apoptosis is the most common and well-studied type of PCD. In this review, we discuss different apoptotic pathways in which plasma membrane and membrane organelles, such as mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomes, and nucleus play the pivotal role. Data concerning caspase cascades involved in these mechanisms are described. Various apoptosis induction mechanisms are analyzed and compared. The close relations between them and the possibility of switching from one pathway to another are demonstrated. In most cases, the result of these pathways is mitochondrial membrane permeabilization and/or caspase activation. These two events are closely linked and serve as the central point of integration of the apoptotic cell death pathways.

We applied a genome-wide microarray analysis to three transgenic mouse models of liver cancer in which targeted overexpression of c-Myc, E2f1, and a combination of the two was driven by the albumin promoter. Although gene expression profiles in HCC derived in all three transgenic lines were highly similar, oncogene-specific gene expression signatures were identified at an early dysplastic stage of hepatocarcinogenesis. Overexpression of E2f1 was associated with a strong alteration in lipid metabolism, and Srebp1was identified as a candidate transcription factor responsible for lipogenic enzyme induction. The molecular signature of c-Myc overexpression included the induction of more than 60 genes involved in the translational machinery that correlated with an increase in liver mass. In contrast, the combined activity of c-Myc and E2f1 specifically enhanced the expression of genes involved in mitochondrial metabolism-particularly the components of the respiratory chain-and correlated with an increased ATP synthesis. Thus, the results suggest that E2f1, c-Myc, and their combination may promote liver tumor development by distinct mechanisms. In conclusion, determination of tissue-specific oncogene expression signatures might be useful to identify conserved expression modules in human cancers. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

The presence of micronuclei in a cell is an indicator of DNA damage and genetic instability. In this review, mechanisms of emergence of micronuclei, their functional activity, and pathways of elimination are discussed. It is supposed that morphological and functional varieties of micronuclei as well as their degradation pathways can be determined by the chromosomal material localized inside these cell structures.

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