Abstract:
:Causes for the complex phenotypes of cancers, such as altered differentiation, invasion and metastasis, are not known, and multigenic defects are likely. In contrast, well-defined deficiencies, such as those affecting DNA-repair mechanisms and enzymatic pathways, are simple, typically caused by one or a few gene mutations. Complementation by introducing defined genetic elements is used to study simple cancer phenotypes, while complementation by the fusion of whole cells is employed occasionally for complex ones. Hybrids formed solely from the common lines (aneuploid due to chromosomal instability, CIN) are rarely reported. We created stable hybrids of two CIN lines, producing a nearly complete genetic sum of the parental karyotypes. Complementation of a simple cancer phenotype, a Fanconi anemia pathway defective in both parental lines, occurred in all hybrids, restoring the normal drug-resistance phenotype. The grossly defective mitotic spindle checkpoint present in both parental lines was partially corrected in some hybrids, supporting a multigenic origin rather than a single gene defect. Using Affymetrix 100K SNP chips, we mapped chromosomal loci differing among the phenotypically distinct hybrid clones. Fusing CIN cell lines to form mapped hybrids offers new tools for positional cloning or classification of simple and complex cancer phenotypes, including mechanical defects and altered drug responses.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Dezentje DA,Arking DE,Kortenhorst MS,West K,Chakravarti A,Kern SEdoi
10.4161/cbt.8.4.7346subject
Has Abstractpub_date
2009-02-01 00:00:00pages
347-55issue
4eissn
1538-4047issn
1555-8576pii
7346journal_volume
8pub_type
杂志文章abstract::Prostate-Specific Membrane Antigen (PSMA) is a glutamate carboxypeptidase II that is highly expressed by both normal and malignant prostate epithelial cells and by the neovasculature of many tumor types but is not expressed by endothelial cells in normal tissue. PSMA possesses the hydrolytic properties of an N-acetyla...
journal_title:Cancer biology & therapy
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pub_type: 杂志文章,随机对照试验
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