Mutations of tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2) genes in metastatic breast cancers

Citation
Ms. Shin et al., Mutations of tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2) genes in metastatic breast cancers, CANCER RES, 61(13), 2001, pp. 4942-4946
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
0008-5472 → ACNP
Volume
61
Issue
13
Year of publication
2001
Pages
4942 - 4946
Database
ISI
SICI code
0008-5472(20010701)61:13<4942:MOTNFA>2.0.ZU;2-0
Abstract
Several lines of evidence suggest that apoptosis dysregulation plays an imp ortant role in cancer metastasis. in this study, to explore the possibility that the mutations of death receptors are involved in the metastasis mecha nism, pie analyzed the death domains of Fas and tumor necrosis factor-relat ed apoptosis-inducing ligand-receptor I and -2 (TRAIL-R1 and -R2) genes for the detection of somatic mutations in 57 breast cancers with (n = 34) or w ithout (n = 23) metastasis to the regional lymph nodes. We found seven muta tions (three TRAIL-R1 and four TRAIL-R2 mutations), and these mutations wer e detected only in the breast cancers with metastasis, Furthermore, we also analyzed the allelic losses of chromosome 8p21-22, where TRAIL-R1 and R2 r eside in the same series of breast cancers, and found that the allelic loss es were significantly higher in metastatic breast cancers., We expressed th e tumor-derived TRAIL-R1 and TRAIL-R2 mutants in 293 cells and found that a poptosis was suppressed. These data suggest that TRAIL-R1 and R2 genes are relevant to the frequent loss of chromosome 8p21-22 in breast cancer and th at the inactivating mutations of TRAIL-R1 and -R2 genes play a role in the metastasis of breast cancer.