期刊
MOLECULAR BIOLOGY
卷 37, 期 2, 页码 170-185出版社
MAIK NAUKA/INTERPERIODICA/SPRINGER
DOI: 10.1023/A:1023381218481
关键词
epithelial tumors; human; chromosome 3 short arm (3p); real-time polymerase chain reaction; methylation; functional testing; extrachromosomal vectors; suppressor genes
Studies of the recent decade, including sequencing of numerous human genome regions, allowed a great progress in detection of new tumor suppressor genes (TSG) and development of new means of their identification and analysis. Effective methods of genome scanning and TSG identification combine DNA array techniques and subtraction hybridization. Alternative ways take advantage of new extrachromosomal vector systems (pETE, pETR) and the functional gene inactivation test. A breakthrough was made in localizing new TSG on the human chromosome 3 short arm, which harbors tumor-suppressing regions and is often rearranged in various tumors and in early carcinogenesis. On 3p, only three putative TSG were known five years ago, and at least ten were identified by the end of 2002. The role of new TSG in carcinogenesis is commonly inferred from a decrease in their transcription in tumor cell lines or primary tumors and from their ability to suppress the tumor growth. Protein products of 3p TGS perform an important function, constraining cell malignization. Some of them are directly involved in regulating the cell cycle and inducing apoptosis (RASSFIA), others suppress angiogenesis (Sema3B) or metastasis (Hyal-1). Numerous attempts to find mutations in exons of silenced genes failed, and at least half of the new candidate genes (RASSFIA, CACNA2D2, BLU, HYAL1, SEMA3B, RAR-beta) proved to be inactivated by promoter methylation.
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