Recently, it has been shown that epigenetic changes are involved in early stages of tumorigenesis, and they may trigger the genetic events leading to tumor development. In cancer epidemiology, there are several epigenetic alterations involved, such as DNA hypermethylation, DNA hypom ...
Primary lung cancer is very heterogeneous in its clinical presentation, histopathology, and treatment response; and like other diseases, the prognosis consists of two essential facets: survival and quality of life (QOL). Lung cancer survival is mostly determined by disease stage and t ...
Breast cancer is a significant cause of morbidity and mortality in the United States. Although breast cancer is more common among White American (WA) women, incidence rates are higher among young African American (AA) women. Approximately 5–10% of all breast cancer can be accounted for by germl ...
Telomeres are distal ends of human chromosomes composed of tandem repeats of the sequence TTAGGG. Possible functions of telomeres include prevention of chromosome degradation, end-to-end fusions, rearrangements, and chromosome loss. Human telomeres in somatic cells undergo p ...
The processes of DNA replication and transcription are intimately affected by the status of chromatin structure. Proteins bind and dissociate at rapid rates in order to control the levels of activity at the genome. Much work has been done over the years to determine the function of transcription ...
Tumor suppressor proteins, like most proteins, require interacting with other proteins in the cell to function properly. These interacting proteins may be regulators or substrates of this tumor suppressor protein. A tumor suppressor protein may also associate with its interacting p ...
Cellular senescence refers to the response of cells to a variety of stimuli, many of which have the potential to induce preneoplastic or neoplastic phenotypes. These stimuli include dysfunctional telomeres, DNA damage, disrupted chromatin structures, the expression of certain onc ...
Many tumor suppressor genes are known to function at least in part through regulation of the transcription of downstream effector genes (Table 1). A major example of such a transcriptional regulator is p53, one of the most commonly mutated tumor suppressor genes in human cancer (1) and hence one of the ...
With the identification and functional characterization of various tumor suppressor genes, the multiprotein pathways in which they function are beginning to be delineated. Mutations in critical pathways, such as the basal cell cycle machinery, DNA surveillance and repair, apopt ...
Gene targeting is the modification of specific DNA sequences in a living organism. Three requirements must be met in order for gene targeting to be successful (1). The process must be directed, so that it affects only the locus of choice. The targeting procedure requires specificity, such that a pred ...
The ability of a tumor suppressor gene to inhibit cell growth is critical for its tumor suppression. Such activity is carried out largely by inducing cell cycle arrest and apoptosis. For example, when the p53 tumor suppressor gene is activated by DNA damage (1), it inhibits the growth of tumor cells by in ...
Determination of cell cycle distribution is an important tool in cell biology. Flow cytometric analysis of cellular DNA can provide rapid quantitative information about DNA ploidy and cell cycle distribution. Presented here are three basic protocols for analysis of DNA by flow cytomet ...
The number of kinases, enzymes whose purpose is to phosphorylate other proteins on serine, threonine, or tyrosine residues, in mammalian cells is presently known to number in the several hundreds or even thousands (1,2). This particular posttranslational modification can dramatica ...
In a noncancerous mammalian cell, the growth-promoting effects of proto-oncogenes are counterbalanced by the growth-constraining effects of tumor suppressor genes (TSGs). The net result is a masterfully orchestrated display of cell proliferation in the absence of tumorigenes ...
About 80% of all human cancers are carcinomas, representing oncogenic transformation of epithelial cells. In-vitro models of epithelial cell transformation are therefore of great interest to elucidate the molecular mechanisms of human cancer. Malignant transformation is a mul ...
The underlying premise of structural biology is that the fundamental understanding of biological functions lies in the three-dimensional structures of proteins and other biopolymers. The two well-established experimental methods for determining the high-resolution str ...
In the early 1970s, Judah Folkman first proposed the hypothesis that tumor growth was dependent on the recruitment of blood vessels, a process called angiogenesis, and that angiogenesis was both an important stage in tumor development and a promising therapeutic target. Based on his observ ...
The transition from normal to cancerous tissue frequently takes years to occur. Epithelial tumors in particular can exist as premalignant lesions for prolonged periods of time, and even then only a low proportion of benign tumors undergo malignant transformation (1,2). Once tumors have f ...
The utilization of mice as a model for human cancer goes back to the generation of inbred laboratory strains in the early twentieth century. Some inbred mouse strains were genetically predisposed to certain types of cancer, providing an early indication that genetic manipulation of a species ...
As interest in cell death has recently increased, many new techniques have been developed to detect and quantitate apoptosis in cells. Multiparameter flow cytometric-based assays provide statistical information on measured parameters at the single-cell level, and are therefore ...