p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts.
Open accessAbstract
It has been shown previously that mutant p53 can act as an immortalizing gene when cotransfected into primary rat embryo fibroblasts along with a selectable marker. To determine whether a mutation at the p53 locus is a common event in the pathways leading to spontaneous cellular immortalization, 11 clonally derived BALB/c murine embryo fibroblast lines were established by passage on a 3T3 schedule and examined for p53 alterations. By the following criteria, all 11 independently established lines contain at least one mutant allele of p53. Seven of these lines have a PAb240-reactive p53 species and exhibit an extended p53 half-life as determined by pulse-chase analysis. The p53 protein species in a subset of these lines is also capable of complex formation with the constitutive heat shock protein hsc70. p53 cytoplasmic DNAs (cDNAs) from several of these lines have been cloned by reverse transcription of cytoplasmic RNA followed by PCR amplification, and the mutations have been mapped by DNA sequence analysis. Point mutation in conserved domains of p53 appears to be a common alteration in these lines, although one established line carries a 24-bp in-frame deletion of p53. The remaining four cell lines do not express detectable p53 protein. For each line there is a different molecular event underlying the lack of p53 expression: (1) deletion of at least the first 6 exons of both p53 alleles; (2) expression of a single p53 mRNA encoding a stop codon at amino acid position 173; (3) no detectable p53 mRNA; and (4) greatly diminished expression of p53 mRNA. These findings indicate that p53 alteration commonly occurs in spontaneously immortalized BALB/c mouse embryo fibroblasts passaged on a 3T3 schedule and, therefore, may be an important event for the immortalization process.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Almost all immortal cell clones that emerge have defects in either p53 or one of its upstream regulators or downstream effectors.
“Almost all of the immortal cell clones that emerge have defects in either p53 or one of its upstream regulators or downstream effectors (16,17)”
From Glycolytic Enzymes Can Modulate Cellular Life Span (2005) · cites this paper as [17]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
DNA sequencing with chain-terminating inhibitors
Sanger, F., Nicklen, S., & Coulson, A. R. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.12.5463 · Cited by 68,572 · see citing works
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508 · see citing works
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876 · see citing works
Germ Line p53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms
Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., et al. (1990) · Science · doi:10.1126/science.1978757 · Cited by 3,765 · see citing works
Mutations in the p53 gene occur in diverse human tumour types
Nigro, J. M., Baker, S. J., Preisinger, A. C., Jessup, J. M., Hosteller, R., Cleary, K. R., Signer, S. H., Davidson, N. E., Baylin, S., Devilee, P., et al. (1989) · Nature · doi:10.1038/342705a0 · Cited by 2,730 · see citing works
Todaro, G. J., & Green, H. (1963) · The Journal of Cell Biology · doi:10.1083/jcb.17.2.299 · Cited by 2,725 · see citing works
The p53 proto-oncogene can act as a suppressor of transformation
Finlay, C. A., Hinds, P. W., & Levine, A. J. (1989) · Cell · doi:10.1016/0092-8674(89)90045-7 · Cited by 1,987 · see citing works
Self-citationSuppression of Human Colorectal Carcinoma Cell Growth by Wild-Type p53
Baker, S. J., Markowitz, S. D., Fearon, E. R., Willson, J. K. V., & Vogelstein, B. (1990) · Science · doi:10.1126/science.2144057 · Cited by 1,742 · see citing works
Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li–Fraumeni syndrome
Srivastava, S. K., Zou, Z., Pirollo, K. F., Blattner, W. A., & Chang, E. H. (1990) · Nature · doi:10.1038/348747a0 · Cited by 1,210 · see citing works
p53: A Frequent Target for Genetic Abnormalities in Lung Cancer
Takahashi, T., Nau, M. M., Chiba, I., Birrer, M. J., Rosenberg, R. K., Vinocour, M., Levitt, M. L., Pass, H. I., Gazdar, A. F., & Minna, J. D. (1989) · Science · doi:10.1126/science.2554494 · Cited by 1,196 · see citing works
Gannon, J., Greaves, R. F., Iggo, R. D., & Lane, D. P. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb08279.x · Cited by 970 · see citing works
p53 Functions as a Cell Cycle Control Protein in Osteosarcomas
Diller, L., Kassel, J., Nelson, C. E., Gryka, M. A., Litwak, G., Gebhardt, M. C., Bressac, B., Öztürk, M., Baker, S. J., Vogelstein, B., et al. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.11.5772 · Cited by 775 · see citing works
Michalovitz, D., Halevy, O., & Oren, M. (1990) · Cell · doi:10.1016/0092-8674(90)90113-s · Cited by 769 · see citing works
Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation
Parada, L. F., Land, H., Weinberg, R. A., Wolf, D., & Rotter, V. (1984) · Nature · doi:10.1038/312649a0 · Cited by 731 · see citing works
Hinds, P. W., Finlay, C. A., & Levine, A. J. (1989) · Journal of Virology · doi:10.1128/jvi.63.2.739-746.1989 · Cited by 595 · see citing works
Self-citationThe relationship between in vitro cellular aging and in vivo human age.
Schneider, E. L., & Mitsui, Y. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.10.3584 · Cited by 569 · see citing works
Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein.Preprint
Martinez, J., Georgoff, I., Martinez, J., & Levine, A. J. (1991) · Genes & Development · doi:10.1101/gad.5.2.151 · Cited by 528 · see citing works
Self-citationGenetic Mechanisms of Tumor Suppression by the Human p53 Gene
Chen, P., Chen, Y., Bookstein, R., & Lee, W. (1990) · Science · doi:10.1126/science.2274789 · Cited by 518 · see citing works
Defining the molecular mechanisms of human cell immortalization
Shay, J. W., Wright, W. E., & Werbin, H. (1991) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/0304-419x(91)90003-4 · Cited by 382 · see citing works
Lehman, T. A., Bennett, W. P., Metcalf, R. A., Welsh, J. A., Ecker, J., Modali, R. V., Ullrich, S. J., Romano, J. W., Appella, E., & Testa, J. R. (1991) · PubMed · Cited by 349 · see citing works
Accumulation of an mRNA and protein in interferon-treated Ehrlich ascites tumour cells
Farrell, P. J., BROEZE, R. J., & Lengyel, P. (1979) · Nature · doi:10.1038/279523a0 · Cited by 330 · see citing works
Finlay, C. A., Hinds, P. W., Tan, T., et al. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.2.531-539.1988 · Cited by 301 · see citing works
Monoclonal antibody analysis of p53 expression in normal and transformed cells
Yewdell, J. W., Gannon, J., & Lane, D. P. (1986) · Journal of Virology · doi:10.1128/jvi.59.2.444-452.1986 · Cited by 261 · see citing works
Hinds, P. W., Finlay, C. A., Frey, A. B., & Levine, A. J. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.8.2863 · Cited by 232 · see citing works
Self-citationp53 Functions as a Cell Cycle Control Protein in Osteosarcomas
Diller, L., Kassel, J., Nelson, C. E., et al. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.11.5772-5781.1990 · Cited by 228 · see citing works
Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer
Branch, N.-N. M. O. (1991) · Lung Cancer · doi:10.1016/0169-5002(91)90309-t · Cited by 209 · see citing works
Goldstein, S., Moerman, E. J., Soeldner, J. S., Gleason, R. E., & Barnett, D. M. (1978) · Science · doi:10.1126/science.622567 · Cited by 190 · see citing works
Tan, T., Wallis, J., & Levine, A. J. (1986) · Journal of Virology · doi:10.1128/jvi.59.3.574-583.1986 · Cited by 159 · see citing works
Self-citationImmortalization of rat embryo fibroblasts by the cellular p53 oncogene.
Rovinski, B., & Benchimol, S. (1988) · PubMed · Cited by 156 · see citing works
The effect of donor age on the in vitro life span of cultured human arterial smooth-muscle cells
Bierman, E. L. (1978) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02616126 · Cited by 147 · see citing works
Limited lifespan in somatic cell hybrids and cybrids
Bunn, C. L., & TARRANT, G. M. (1980) · Experimental Cell Research · doi:10.1016/0014-4827(80)90443-7 · Cited by 124 · see citing works
Expression of SV40 T antigen in finite life-span hybrids of normal and SV40-transformed fibroblasts
Pereira‐Smith, O. M., & Smith, J. R. (1981) · Somatic Cell and Molecular Genetics · doi:10.1007/bf01542986 · Cited by 124 · see citing works
Direct sequencing from low-melt agarose with Sequenase@
Kretz, K. A., Carson, G. S., & O’Brien, J. S. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.14.5864 · Cited by 118 · see citing works
The p53 cellular tumor antigen: gene structure, expression and protein properties
Oren, M. (1985) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/0304-419x(85)90015-0 · Cited by 108 · see citing works
Spontaneous Immortalization Rate of Cultured Chinese Hamster Cells2
Kraemer, P. M., Ray, F. A., Brothman, A. R., Barthoidi, M. F., & Cram, L. S. (1986) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/76.4.703 · Cited by 58 · see citing works
Biological and Molecular Analysis of P53 Cellular-Encoded Tumor Antigen
Rotter, V., & Wolf, D. (1985) · Advances in cancer research · doi:10.1016/s0065-230x(08)60944-6 · Cited by 55 · see citing works
Increased expression of mutant forms of p53 oncogene in primary lung cancer
Unit, H. A. I. O. (1990) · Lung Cancer · doi:10.1016/0169-5002(90)90155-f · Cited by 45 · see citing works
Common Mechanisms Of Transformation By Small DNA Tumor Viruses
Villarreal, L. P. (1989) · Medical Entomology and Zoology · Cited by 36 · see citing works
Oren, M., Reich, N. C., & Levine, A. J. (1982) · Molecular and Cellular Biology · doi:10.1128/mcb.2.4.443-449.1982 · Cited by 36 · see citing works
Self-citationCulture conditions induce the appearance of immortalized C3H mouse cell lines
Curatolo, L., Erba, E., & Morasca, L. (1984) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02619607 · Cited by 28 · see citing works
Genetic and Molecular Studies of Cellular Immortalization
Smith, J. R., & Pereira‐Smith, O. M. (1990) · Advances in cancer research · doi:10.1016/s0065-230x(08)60808-8 · Cited by 17 · see citing works
Wolf, D., Admon, S., Oren, M., et al. (1984) · Molecular and Cellular Biology · doi:10.1128/mcb.4.3.552-558.1984 · Cited by 15 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- 9 1988. Genetic analysis of indefinite division in human cells: Identification of 4 complementation groups. Proc. Nat1. Acad. Sci. 85: 6042-6046.
- Rohme, D. 1981. Evidence for a relationship between longevity of mammalian species and life spans of normal fibroblasts in v~tro and erythrocytes in vivo. Proc. Natl. Acad. Sci. 78: 5009-5013.
- Selden, R.F. 1987a. Southern blotting and hybridization. In Cur- rent protocols in molecular biology (ed. F.M. Ausubel, R.E. Kingston, D.D. Moore, J.G. Seidman, I.A. Smith, and K. Struhl), pp. 2.9.1-2.9.10., Greene/Wiley-Interscience, New York. 1987b. Analysis of RNA by Northern hybridization. In Current protocols in molecular biology (ed. F.M. Ausubel, R.E. Kingston, D.D. Moore, J.G. Seidman, J.A. Smith, and K. Struhll, pp. 4.9.1-4.9.8., Greene/Wiley-Interscience, New York.
Cited by
Sorted by citations
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · see citing works
Momand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90644-r · Cited by 3,113 · see citing works
Self-citationTelomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108 · see citing works
The p53-mdm-2 autoregulatory feedback loop.
Wu, X., Bayle, J. H., Olson, D., & Levine, A. J. (1993) · Genes & Development · doi:10.1101/gad.7.7a.1126 · Cited by 1,801 · see citing works
Self-citationThe RB and p53 pathways in cancer
Sherr, C. J., & McCormick, F. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00102-2 · Cited by 1,690 · see citing works
Tumor Suppression at the Mouse INK4a Locus Mediated by the Alternative Reading Frame Product p19
Kamijo, T., Zindy, F., Roussel, M. F., Quelle, D. E., Downing, J. R., Ashmun, R. A., Grosveld, G., & Sherr, C. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80452-3 · Cited by 1,566 · see citing works
The coordinate regulation of the p53 and mTOR pathways in cells
Feng, Z., Zhang, H., Levine, A. J., & Jin, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502857102 · Cited by 1,235 · see citing works
Self-citationForging a signature of in vivo senescence
Sharpless, N. E., & Sherr, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3960 · Cited by 1,104 · see citing works
Rules for Making Human Tumor Cells
Hahn, W. C., & Weinberg, R. A. (2002) · New England Journal of Medicine · doi:10.1056/nejmra021902 · Cited by 951 · see citing works
Gain of function mutations in p53
Dittmer, D., Pati, S., Zambetti, G., Chu, S., Teresky, A. K., Moore, M., Finlay, C., & Levine, A. J. (1993) · Nature Genetics · doi:10.1038/ng0593-42 · Cited by 894 · see citing works
Self-citationFunctional and physical interactions of the ARF tumor suppressor with p53 and Mdm2
Kamijo, T., Weber, J. D., Zambetti, G., Zindy, F., Roussel, M. F., & Sherr, C. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.8292 · Cited by 899 · see citing works
Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
Eischen, C. M., Weber, J. D., Roussel, M. F., Sherr, C. J., & Cleveland, J. L. (1999) · Genes & Development · doi:10.1101/gad.13.20.2658 · Cited by 819 · see citing works
Tuveson, D. A., Shaw, A. T., Willis, N. A., Silver, D. P., Jackson, E. L., Chang, S., Mercer, K. L., Grochow, R., Hock, H., Crowley, D., et al. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00085-6 · Cited by 798 · see citing works
Ribeiro, R. C., Sandrini, F., Figueiredo, B., Zambetti, G. P., Michalkiewicz, E., Lafferty, A. R., DeLacerda, L., Rabin, M., Cadwell, C., Sampaio, G., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161479898 · Cited by 541 · see citing works
Different telomere damage signaling pathways in human and mouse cells
Smogorzewska, A., & de Lange, T. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf433 · Cited by 482 · see citing works
BID regulation by p53 contributes to chemosensitivity
Sax, J. K., Fei, P., Murphy, M. E., Bernhard, E., Korsmeyer, S. J., & El-Deiry, W. S. (2002) · Nature Cell Biology · doi:10.1038/ncb866 · Cited by 420 · see citing works
Dannenberg, J.-H., van Rossum, A., Schuijff, L., & te Riele, H. (2000) · Genes & Development · doi:10.1101/gad.847700 · Cited by 413 · see citing works
DAP kinase activates a p19ARF/p53-mediated apoptotic checkpoint to suppress oncogenic transformation
Raveh, T., Droguett, G., Horwitz, M. S., DePinho, R. A., & Kimchi, A. (2001) · Nature Cell Biology · doi:10.1038/35050500 · Cited by 361 · see citing works
p53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer
Tschaharganeh, D. F., Xue, W., Calvisi, D. F., Evert, M., Michurina, T. V., Dow, L. E., Banito, A., Katz, S. F., Kastenhuber, E. R., Weissmueller, S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.051 · Cited by 227 · see citing works
Wide spectrum of tumors in knock‐in mice carrying a Cdk4 protein insensitive to INK4 inhibitors
Sotillo, R., Dubus, P., Martn, J., de la Cueva, E., Ortega, S., Malumbres, M., & Barbacid, M. (2001) · The EMBO Journal · doi:10.1093/emboj/20.23.6637 · Cited by 208 · see citing works
Melk, A., Kittikowit, W., Sandhu, I., Halloran, K. M., Grimm, P., Schmidt, B. M. W., & Halloran, P. F. (2003) · Kidney International · doi:10.1046/j.1523-1755.2003.00032.x · Cited by 205 · see citing works
Pantoja, C., & Serrano, M. (1999) · Oncogene · doi:10.1038/sj.onc.1202880 · Cited by 201 · see citing works
Superoxide Dismutase 1 Knock-down Induces Senescence in Human Fibroblasts
Blander, G., de Oliveira, R. M., Conboy, C. M., Haigis, M., & Guarente, L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307146200 · Cited by 183 · see citing works
p53 represses ribosomal gene transcription
Budde, A., & Grummt, I. (1999) · Oncogene · doi:10.1038/sj.onc.1202402 · Cited by 157 · see citing works
Identification of Proteins Associated with Murine Cytomegalovirus Virions
Kattenhorn, L. M., Mills, R., Wagner, M., Lomsadze, A., Makeev, V., Borodovsky, M., Ploegh, H. L., & Kessler, B. M. (2004) · Journal of Virology · doi:10.1128/jvi.78.20.11187-11197.2004 · Cited by 147 · see citing works
Boregowda, S. V., Krishnappa, V., Chambers, J. W., Lograsso, P. V., Lai, W., Ortiz, L. A., & Phinney, D. G. (2012) · STEM CELLS · doi:10.1002/stem.1069 · Cited by 114 · see citing works
p53 protein accumulation and gene mutations in human glioma cell lines
Anker, L., Ohgaki, H., Ludeke, B. I., Herrmann, H., Kleihues, P., & Westphal, M. (1993) · International Journal of Cancer · doi:10.1002/ijc.2910550618 · Cited by 66 · see citing works
Sax, J. K., & El-Deiry, W. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303191200 · Cited by 60 · see citing works
- Authors
- Harvey, D. M., & Levine, A. J.
- Affiliations
- Princeton University (US)
- ORCID
- Levine, A J
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1991-12-01
- Volume
- 5
- Issue
- 12b
- Pages
- 2375-2385
- ISSN
- 0890-9369 (ISSN-L)
- OpenAlex
- W2131675463
- Cited by
- 453
- References
- 42
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 4 · 2021: 9 · 2020: 10 · 2019: 4 · 2018: 8 · 2017: 7 · 2016: 11 · 2015: 7 · 2014: 12 · 2013: 12 · 2012: 10
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (5t32gm007312-23)
- National Institute of General Medical Sciences (5 T32 GM07312-16)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- TP53 mutation, spontaneous immortalization, embryonic fibroblasts, BALB/c mice, p53 point mutations, p53 deletion, p53 mRNA expression
- MeSH terms
- Animals, Base Sequence, Cell Line, Cell Separation, Embryo, Mammalian, Fibroblasts, Half-Life, Mice, Inbred BALB C, Molecular Sequence Data, Mutation, Selection, Genetic, Transfection, Tumor Suppressor Protein p53, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
