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Titolo:
LOCALIZATION OF TUMOR-SUPPRESSOR ACTIVITY IMPORTANT IN NONSMALL CELL LUNG-CARCINOMA ON CHROMOSOME 11Q
Autore:
MURAKAMI Y; NOBUKUNI T; TAMURA K; MARUYAMA T; SEKIYA T; ARAI Y; GOMYOU H; TANIGAMI A; OHKI M; CABIN D; FRISCHMEYER P; HUNT P; REEVES RH;
Indirizzi:
NATL CANC CTR,RES INST,DIV ONCOGENE,CHUO KU,5-1-1 TSUKJI TOKYO 1040045 JAPAN NATL CANC CTR,RES INST,DIV RADIOBIOL TOKYO 1040045 JAPAN JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL BALTIMORE MD 21205
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 14, volume: 95, anno: 1998,
pagine: 8153 - 8158
SICI:
0027-8424(1998)95:14<8153:LOTAII>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
YEAST ARTIFICIAL CHROMOSOME; MALIGNANT PHENOTYPE; DNA-SEQUENCE; CANCER; LINE; HETEROZYGOSITY; DELETION; LOCUS; GENE; TRANSFORMATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
Y. Murakami et al., "LOCALIZATION OF TUMOR-SUPPRESSOR ACTIVITY IMPORTANT IN NONSMALL CELL LUNG-CARCINOMA ON CHROMOSOME 11Q", Proceedings of the National Academy of Sciences of the United Statesof America, 95(14), 1998, pp. 8153-8158

Abstract

Loss of heterozygosity on chromosome 11q23 is observed at high frequency in human nonsmall cell lung carcinomas (NSCLCs), suggesting the presence of a tumor suppressor gene. Previous analysis of DNA from 79 patients identified a commonly deleted segment of 5 centimorgans. Complementation analysis was used to further localize a putative tumor suppressor gene. Three yeast artificial chromosome (YAC) clones spanning the minimal loss of heterozygosity region were modified, and spheroplastfusion was used to transfer them into human A549 NSCLC or murine Lewis lung carcinoma (LLC) cell fines. The resulting yeast x human hybrid cell lines containing an intact copy of a 1.6-Mb YAC, 939b12, showed reduced growth in vitro. Injection of parental A549 cells into athymic (nu/nu) mice resulted in tumor formation at 27 of 28 injection sites. In contrast, two independent 939b12-containing cell lines formed tumors at only 3 of 20 injection sites. 939b12 also suppressed tumor formation by LLC NSCLC cells in nude mice, but YACs 785e12 and 911f2, which flank 939b12, had no suppressor activity. Further localization of tumor suppression activity on 939b12 was accomplished by introduction of defined fragmentation derivatives into A549 cells and by analysis of YACs that were broken on transfer into LLC cells. This complementation approach localized tumor suppression activity to the central 700 kb of 939b12 and provides a functional assay for positional cloning of this tumor suppressor gene.

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Documento generato il 31/03/20 alle ore 10:28:57