期刊
CANCER BIOLOGY & THERAPY
卷 3, 期 12, 页码 1313-1321出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.3.12.1459
关键词
tuberous sclerosis; von Hippel-Lindau; renal cancer; microarrays; gene expression profiling
类别
资金
- NCI NIH HHS [N01 CN-95037, CA-06927] Funding Source: Medline
Background: The inherently complex signaling networks of tumors result from genetic and epigenetic alterations that occur during cancer initiation and progression. Methods: In an attempt to identify early molecular changes associated with dominantly inherited predisposition to two-hit renal tumors, the expression profiles of primary cultures of phenotypically normal renal epithelial cells from individuals bearing a germline mutation in either the von Hippel-Lindau (VHL) or the tuberous sclerosis complex (TSC) gene were compared to that of renal epithelial cells from control nonmutation carriers by microarray analysis. Results: Reliability of the microarray data from pooled samples was confirmed by real-time RT-PCR. Principal Component Analysis revealed substantial differences in the gene expression profiles of the renal epithelial cells from VHL and TSC mutation carriers. In several instances, the microarray data confirm our present knowledge of the cellular pathways affected by biallelic VHL and TSC mutations. Conclusions: These findings demonstrate that heterozygosity for a mutant tumor suppressor gene may alter the expression profiles of phenotypically normal epithelial cells in a gene-specific manner. Detectable effects of one-hit represent early molecular changes in tumorigenesis that may serve as targets for chemopreventive intervention.
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