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.
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
Richard A
RA
Woo
Randy Y C
RY
Poon
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