Abstract
The machinery of the cell cycle provides a mechanism for the duplication of cellular DNA during cell division and the appropriate distribution of this DNA to resulting daughter cells. It is important for cell survival that this process occurs in a highly regulated and controlled manner to ensure the accurate transmission of genetic material. Dividing eukaryotic cells are equipped with surveillance mechanisms to ensure that cell cycle progression does not occur if conditions are inappropriate, for example, if DNA is damaged or nucleotide supplies are limiting. These mechanisms have collectively been referred to as checkpoint control. Failure of checkpoint control leads to inappropriate cell division and the accumulation of DNA damage that is the hallmark of human tumor cells [4, 5].
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS 3rd, Johnson BE, Skolnick MH (1994) A cell cycle regulator potentially involved in the genesis of many tumor types. Science 264: 344–345
Larsen CJ (1997) Contribution of the dual coding capacity of the p16INK4a/MTS1/ CDKN2 locus to human malignancies. Prog Cell Cycle Res 3: 109–124
Serrano M, Hannon GJ, Beach D (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366: 704–707
Hartwell LH, Kastan MB (1994) Cell cycle control and cancer. Science 266: 1821–1828
Hartwell L (1992) Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells. Cell 71: 543–546
Murray AW (1994) Cyclin dependent kinases: regulators of the cell cycle and more. Current Biology 1: 191–195
Pines J (1995) Cyclins and cyclin-dependent kinases: Theme and variations. Adv in Cancer Res 66: 181–212
Lukas J, Bartkova J, Rohde M, Strauss M, Bartek J (1995) Cyclin D1 is dispensible for G1 control in retinoblastoma gene-deficient cells independently of cdk4 activity. Mol Cell Biol 15: 2600–2611
Sherr CJ, Roberts JM (1995) Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 9: 1149–1163
Serrano M (1997) The tumor suppressor protein p16INK4a. Exp Cell Res 7–13
Quelle DE, Zindy F, Ashmun RA, Sherr CJ (1995) Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell 83: 993–1000
Chin L, Pomerantz J, DePinho RA (1998) The INK4a/ARF tumor suppressor gene — two products — two pathways. Trends Biochem Sci 23: 291–296
Pomerantz J, Schreiber-Agus N, Liegeois NJ, Silverman A, Alland L, Chin L, Potes J, Chen K, Orlow I, Lee HW, Cordon-Cardo C, DePinho RA (1998) The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2’s inhibition of p53. Cell 92: 713–723
Zhang Y, Xiong Y, Yarbrough WG (1998) ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92: 725–734
Gazzeri S, Della Valle V, Chaussade L, Brambilla C, Larsen CJ, Brambilla E (1998) The human p19ARF protein encoded by the beta transcript of the p16INK4a gene is frequently lost in small cell lung cancer. Cancer Res 58: 3926–3931
Vonlanthen S, Heighway J, Tschan MP, Borner MM, Altermatt HJ, Kappeler A, Tobler A, Fey MF, Thatcher N, Yarbrough WG, Betticher DC (1998) Expression of pl6INK4a/ p16a and p19ARF/p16(3 is frequently altered in non-small cell lung cancer and correlates with p53 overexpression. Oncogene 17: 2779–2785
Gorgoulis VG, Zacharatos P, Kotsinas A, Liloglou T, Kyroudi A, Veslemes M, Rassidakis A, Halazonitis TD, Field JK, Kittas C (1998) Alterations of the p16-pRb pathway and the chromosome locus 9p21–22 in non-small-cell lung carcinomas: Relationship with p53 and MDM2 protein expression. Am J Pathol 153: 1749–1765
Serrano M, Gomez-Lahoz E, DePinho RA, Beach D, Bar-Sagi D (1995) Inhibition of ras-induced proliferation and cellular transformation by p16INK4. Science 267: 249–252
Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW (1997) Oncogenic ras promotes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88: 593–602
Haas K, Staller P, Geisen C, Bartek J, Eilers M, Moroy T (1997) Mutual requirement of CDK4 and Myc in malignant transformation: evidence for cyclin D1/CDK4 and P16INK4a as upstream regulators of Myc. Oncogene 15: 179–192
Medema RH, Herrara RE, Lam P, Weinberg RA (1995) Growth suppression by pl6ink4 requires functional retinoblastoma protein. Proc Natl Acad Sci USA 92: 6289–6293
Jin X, Nguyen D, Zhang WW, Kyritsis AP, Roth JA (1995) Cell cycle arrest and inhibition of tumor cell proliferation by the p16INK4 gene mediated by an adenovirus vector. Cancer Res 55: 3250–3253
Spillare EA, Okamoto A, Hagiwara K, Demetrick DJ, Serrano M, Beach D, Harris CC (1996) Suppression of growth in vitro and tumorigenicity in vivo of human carcinoma cell lines by transfected p16INK4. Mol Carcinog 16: 53–60
Craig C, Kim M, Ohri E, Wersto R, Katayose D, Li Z, Choi YH, Mudahar B, Srivastava S, Seth P, Cowan K (1997) Effects of the adenovirus-mediated p16INK4A expression on cell cycle arrest are determined by endogenous p16 and Rb status in human cancer cells. Oncogene 16: 265–272
Gossen M, Bujard H (1992) Tight control of gene expression in mammalian cells by tetracycline responsive promoters. Proc Natl Acad Sci USA 89: 5547–5551
Alemany R, Ruan S, Kataoka M, Koch PE, Mukhopadhyay T, Cristiano RJ, Roth JA, Zhang WW (1996) Growth inhibitory effect of anti-K-ras adenovirus on lung cancer cells. Cancer Gene Ther 3: 296–301
Dykes DJ, Abbott BJ, Mayo JG, Harrison Jr SD, Laster Jr WR, Simpson-Herren L, Griswold Jr DP (1992) Development of human tumor xenograft models for in vivo evaluation of new antitumor drugs. Contrib Oncol 42: 1–22
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer Basel AG
About this paper
Cite this paper
Burton, C.A., Boylan, J., Robinson, C., Kerr, J., Benfield, P. (2000). Constitutive expression of a tumor suppressor leads to tumor regression in a xenograft model. In: Letts, L.G., Morgan, D.W. (eds) Inflammatory Processes:. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8468-6_6
Download citation
DOI: https://doi.org/10.1007/978-3-0348-8468-6_6
Publisher Name: Birkhäuser, Basel
Print ISBN: 978-3-0348-9580-4
Online ISBN: 978-3-0348-8468-6
eBook Packages: Springer Book Archive