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P53 MUTATIONS IN HUMAN IMMORTALIZED EPITHELIAL-CELL LINES
Author(s): LEHMAN TA, MODALI R, BOUKAMP P, STANEK J, BENNETT WP, WELSH JA, METCALF RA, STAMPFER MR, FUSENIG N, ROGAN EM, HARRIS CC
Source: CARCINOGENESIS    Volume: 14    Issue: 5    Pages: 833-839    Published: MAY 1993  
Times Cited: 217     References: 79     
Abstract: Although rodent celts have been immortalized following transfection with a mutant p53 gene, the role of p53 in the immortalization of human cells is unknown. Therefore, human epithelial cell tines were examined for p53 mutations in exons 4-9 which include the evolutionarily conserved regions. A spontaneously immortalized skin keratinocyte cell line, HaCat, and three ras-transfected clones, have a p53 mutational spectrum that is typical of ultraviolet light induced mutations. A normal finite lifespan cell strain (184) and two benzo[a]pyrene immortalized mammary epithelial cell lines derived from 184 (184A1 and 184B5) contain wild type p53 sequences in exons 4-9, although elevated levels of nuclear p53 indicate an alteration in the stability of the normally transient protein. Wild type p53 was found in human bronchial, esophageal and hepatic epithelial cells immortalized by SV40 T antigen gene and human renal epithelial cells immortalized by adenovirus 5. BEAS-2B, an SV40 T antigen immortalized bronchial epithelial cell line and two subclones, have a germline polymorphism at codon 47. Inactivation of p53 by mechanisms such as mutation or complexing with proteins of DNA tumor viruses appears to be important in the immortalization of human epithelial celts.
Document Type: Article
Language: English
Reprint Address: LEHMAN, TA (reprint author), BIOSERVE BIOTECHNOL LTD, LAUREL, MD 20707 USA
Addresses:
1. LAWRENCE BERKELEY LAB, BERKELEY, CA 94720 USA
2. GERMAN CANC RES CTR, W-6900 HEIDELBERG 1, GERMANY
3. NCI, HUMAN CARCINOGENESIS LAB, BETHESDA, MD 20892 USA
4. CHILDRENS MED RES INST, WESTMEAD, NSW AUSTRALIA
Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP
Subject Category: Oncology
IDS Number: LD408
ISSN: 0143-3334
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