Gene mutations and aneuploidy: the instability that causes cancer.
Cancer cells have been characterized with activated mutant oncogenes and inactivated or deleted tumor suppressor genes. Cancer cells are also aneuploid, displaying a jumble of chromosomal anomalies including gain or loss of whole chromosomes or transposed chromosomal fragments. Whether mutation of specific genes or aneuploidy is more critical for tumorigenesis is very much a contentious issue. We recently showed that activated oncogenes induce oxidative damage that is exacerbated by conventional cell culture conditions. This "culture shock" or a loss of p53 function creates a precarious environment that permits oncogenes to induce rapid chromosomal instability and transformation. We found that mutant genes and aneuploidy were prerequisites and collaborators for neoplastic transformation.
Woo
Richard A
RA
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
Poon
Randy Y C
RY
D000782:Aneuploidy; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D043171:Chromosomal Instability / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D016159:Tumor Suppressor Protein p53