TAILIEUCHUNG - Endocrinology Basic and Clinical Principles - part 8

Bảng 2 gen đại diện ức chế khối u trong khối u Nhân 5p nội địa hóa nhiễm sắc thể 10Q 11p 11q 13q 17p Tên locus APC - WT-1 Menin Rb-1 khối u p53 có liên quan đến polyposis polyp tuyến gia đình, MEN ung thư biểu mô colotectal 2, | Chapter 19 Oncogenes and Tumor Suppressor Genes 303 Table 2 Representative Tumor suppressor Genes in Human Tumors a Chromosomal localization Name of locus Tumors involved Properties of gene product 5p APC Familial adenomatous polyposis colotectal carcinoma Cytoplasmic protein 10q MEN 2 astrocytoma 11p WT-1 Wilms tumor rhabdomyo- sarcoma hepatoblastoma bladder and lung carcinoma DNA-binding protein 11q Menin MEN 1 Transcription factor 13q Rb-1 Retinoblastoma osteosarcoma breast and bladder carcinoma DNA-binding protein 17p p53 Small-cell and squamous cell lung carcinoma breast carcinoma colorectal carcinoma and other DNA-binding protein 17q NF-1 Neurofibromatosis type 1 Induces GTP hydrolysis of ras protein 18q DCC Colorectal carcinoma Cell-surface receptor Adapted from Weinberg 1994 . when injected into suitable hosts unless specific chromosomes were lost from the hybrids. This phenomenon of tumor suppression suggested that recessive genetic changes were responsible for the tumorigenic phenotype. Although cell hybrid studies of tumor suppression provided very useful information on chromosomal assignment this method could not lead to gene identification and to date no suppressor gene thus has been isolated. The identification of tumor suppressor genes has been greatly facilitated through studies of familial cancers. This is best illustrated in the identification and isolation of the retinoblastoma susceptibility gene Rb . The essential features of retinoblastoma are that in the familial forms of the tumor the affected individual inherits a mutant loss-of-function allele from an affected parent and a second somatic mutation inactivates the normal allele derived from the unaffected parent. By contrast the sporadic forms of the tumor involve two somatic mutational events. According to this recessive mutation model homozygous deletion of the Rb gene would be expected in some tumors and Rb gene expression could be altered in retinoblastoma compared to normal tissue. .

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