| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892
p27Kip1, a cyclin-dependent kinase inhibitor, is recognized as a negative regulator of the cell cycle. In this paper, we report that overexpression of p27Kip1 triggers apoptosis in several different human cancer cell lines. Using a recombinant adenoviral vector that expresses p27Kip1 (Adp27), we found that overexpression of p27Kip1 in MDA-MB-231 breast cancer cells induces apoptosis that was seen by a number of different techniques, including flow cytometry and in situ terminal deoxynucleotidyl transferase-mediated nick end labeling, flow cytometric assay for sub-G1 population, and 4',6-diamindino-2-phenylindole staining. Cleavage of poly-(ADP-ribose) polymerase and degradation of cyclin B1, events that are known to be associated with apoptosis, were also observed following overexpression of p27Kip1. This is the first report indicating a role for p27Kip1 in induction of apoptosis.
1 To whom requests for reprints should be addressed, at Medical Breast Cancer Section, Medicine Branch, National Cancer Institute, NIH, Building 10, Room 12N226, Bethesda, MD 20892. Phone: (301) 496-9517; Fax: (301) 402-0172; E-mail: pseth@boxp.nih.gov.
Received 9/12/97. Accepted 10/30/97.
This article has been cited by other articles:
|
|
 |
|
  Z. Wang, B. W. Yu, K. W. Rahman, F. Ahmad, and F. H. Sarkar Induction of growth arrest and apoptosis in human breast cancer cells by 3,3-diindolylmethane is associated with induction and nuclear localization of p27kip Mol. Cancer Ther., February 1, 2008; 7(2): 341 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Filipits, R. Pirker, A. Dunant, S. Lantuejoul, K. Schmid, A. Huynh, V. Haddad, F. Andre, R. Stahel, J.-P. Pignon, et al. Cell Cycle Regulators and Outcome of Adjuvant Cisplatin-Based Chemotherapy in Completely Resected Non-Small-Cell Lung Cancer: The International Adjuvant Lung Cancer Trial Biologic Program J. Clin. Oncol., July 1, 2007; 25(19): 2735 - 2740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Cardoso, V. Durbecq, J.-F. Laes, B. Badran, L. Lagneaux, F. Bex, C. Desmedt, K. Willard-Gallo, J. S. Ross, A. Burny, et al. Bortezomib (PS-341, Velcade) increases the efficacy of trastuzumab (Herceptin) in HER-2-positive breast cancer cells in a synergistic manner Mol. Cancer Ther., December 1, 2006; 5(12): 3042 - 3051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. I. Shapiro Cyclin-Dependent Kinase Pathways As Targets for Cancer Treatment J. Clin. Oncol., April 10, 2006; 24(11): 1770 - 1783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. R. Jarnagin, D. S. Klimstra, M. Hezel, M. Gonen, Y. Fong, K. Roggin, K. Cymes, R. P. DeMatteo, M. D'Angelica, L. H. Blumgart, et al. Differential Cell Cycle-Regulatory Protein Expression in Biliary Tract Adenocarcinoma: Correlation With Anatomic Site, Pathologic Variables, and Clinical Outcome J. Clin. Oncol., March 1, 2006; 24(7): 1152 - 1160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Y. Wu, S. E. Wang, M. E. Sanders, I. Shin, F. Rojo, J. Baselga, and C. L. Arteaga Reduction of Cytosolic p27Kip1 Inhibits Cancer Cell Motility, Survival, and Tumorigenicity Cancer Res., February 15, 2006; 66(4): 2162 - 2172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hu, X. Wang, L. Zeng, D.-Y. Cai, K. Sabapathy, S. P. Goff, E. J. Firpo, and B. Li ERK Phosphorylates p66shcA on Ser36 and Subsequently Regulates p27kip1 Expression via the Akt-FOXO3a Pathway: Implication of p27kip1 in Cell Response to Oxidative Stress Mol. Biol. Cell, August 1, 2005; 16(8): 3705 - 3718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wang, D. Xia, N. Li, C. Wang, T. Chen, T. Wan, G. Chen, and X. Cao Bone Marrow Stromal Cell-derived Growth Inhibitor Inhibits Growth and Migration of Breast Cancer Cells via Induction of Cell Cycle Arrest and Apoptosis J. Biol. Chem., February 11, 2005; 280(6): 4374 - 4382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Eguchi, S Carpentier, S S Kim, and S F Moss p27kip1 regulates the apoptotic response of gastric epithelial cells to Helicobacter pylori Gut, June 1, 2004; 53(6): 797 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Eymin and E. Brambilla The yin and the yang of p27Kip1 as a target for cancer therapy Eur. Respir. J., May 1, 2004; 23(5): 663 - 664. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Chandramohan, S. Jeay, S. Pianetti, and G. E. Sonenshein Reciprocal Control of Forkhead box O 3a and c-Myc via the Phosphatidylinositol 3-Kinase Pathway Coordinately Regulates p27Kip1 Levels J. Immunol., May 1, 2004; 172(9): 5522 - 5527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsunobu, K. Tanaka, Y. Matsumoto, F. Nakatani, R. Sakimura, M. Hanada, X. Li, Y. Oda, I. Naruse, H. Hoshino, et al. The Prognostic and Therapeutic Relevance of p27kip1 in Ewing's Family Tumors Clin. Cancer Res., February 1, 2004; 10(3): 1003 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jiang, C. B. Matranga, D. Cai, V. M. Latham Jr., X. Zhang, A. M. Lowell, F. Martelli, and G. I. Shapiro Flavopiridol-Induced Apoptosis during S Phase Requires E2F-1 and Inhibition of Cyclin A-Dependent Kinase Activity Cancer Res., November 1, 2003; 63(21): 7410 - 7422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pohl, M. Rudas, O. Dietze, S. Lax, E. Markis, R. Pirker, C. C. Zielinski, H. Hausmaninger, E. Kubista, H. Samonigg, et al. High p27Kip1 Expression Predicts Superior Relapse-Free and Overall Survival for Premenopausal Women With Early-Stage Breast Cancer Receiving Adjuvant Treatment With Tamoxifen Plus Goserelin J. Clin. Oncol., October 1, 2003; 21(19): 3594 - 3600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Eguchi, N. Herschenhous, N. Kuzushita, and S. F. Moss Helicobacter pylori Increases Proteasome-mediated Degradation of p27kip1 in Gastric Epithelial Cells Cancer Res., August 1, 2003; 63(15): 4739 - 4746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Narayanan, M. S. Condon, M. C. Bosland, N. K. Narayanan, and B. S. Reddy Suppression of N-Methyl-N-nitrosourea/Testosterone-induced Rat Prostate Cancer Growth by Celecoxib: Effects on Cyclooxygenase-2, Cell Cycle Regulation, and Apoptosis Mechanism(s) Clin. Cancer Res., August 1, 2003; 9(9): 3503 - 3513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Daneshmand, D. A. E. Parolin, H. W. Hirte, P. Major, G. Goss, D. Stewart, G. Batist, W. H. Miller Jr., S. Matthews, L. Seymour, et al. A Pharmacodynamic Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor ZD1839 in Metastatic Colorectal Cancer Patients Clin. Cancer Res., July 1, 2003; 9(7): 2457 - 2464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sarkar, M. Leszczyniecka, D.-c. Kang, I. V. Lebedeva, K. Valerie, S. Dhar, T. K. Pandita, and P. B. Fisher Down-regulation of Myc as a Potential Target for Growth Arrest Induced by Human Polynucleotide Phosphorylase (hPNPaseold-35) in Human Melanoma Cells J. Biol. Chem., June 27, 2003; 278(27): 24542 - 24551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Wei, W. K. Miskimins, and R. Miskimins The Sp1 Family of Transcription Factors Is Involved in p27Kip1-Mediated Activation of Myelin Basic Protein Gene Expression Mol. Cell. Biol., June 15, 2003; 23(12): 4035 - 4045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Z. Rassidakis, F.-X. Claret, R. Lai, Q. Zhang, A. H. Sarris, T. J. McDonnell, and L. J. Medeiros Expression of p27Kip1 and c-Jun Activation Binding Protein 1 Are Inversely Correlated in Systemic Anaplastic Large Cell Lymphoma Clin. Cancer Res., March 1, 2003; 9(3): 1121 - 1128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Filipits, G. Pohl, T. Stranzl, H. Kaufmann, J. Ackermann, H. Gisslinger, H. Greinix, A. Chott, and J. Drach Low p27Kip1 Expression Is an Independent Adverse Prognostic Factor in Patients with Multiple Myeloma Clin. Cancer Res., February 1, 2003; 9(2): 820 - 826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hoos, A. Nissan, A. Stojadinovic, J. Shia, C. V. Hedvat, D. H. Y. Leung, P. B. Paty, D. Klimstra, C. Cordon-Cardo, and W. D. Wong Tissue Microarray Molecular Profiling of Early, Node-negative Adenocarcinoma of the Rectum: A Comprehensive Analysis Clin. Cancer Res., December 1, 2002; 8(12): 3841 - 3849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-a. Masuda, H. Inoue, H. Sonoda, S. Mine, Y. Yoshikawa, K. Nakayama, K.-I. Nakayama, and M. Mori Clinical and Biological Significance of S-Phase Kinase-associated Protein 2 (Skp2) Gene Expression in Gastric Carcinoma: Modulation of Malignant Phenotype by Skp2 Overexpression, Possibly via p27 Proteolysis Cancer Res., July 1, 2002; 62(13): 3819 - 3825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vanzulli, A. Efeyan, F. Benavides, L. A. Helguero, G. Peters, J. Shen, C. J. Conti, C. Lanari, and A. Molinolo p21, p27 and p53 in estrogen and antiprogestin-induced tumor regression of experimental mouse mammary ductal carcinomas Carcinogenesis, May 1, 2002; 23(5): 749 - 758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Muraoka, A. E. G. Lenferink, B. Law, E. Hamilton, D. M. Brantley, L. R. Roebuck, and C. L. Arteaga ErbB2/Neu-Induced, Cyclin D1-Dependent Transformation Is Accelerated in p27-Haploinsufficient Mammary Epithelial Cells but Impaired in p27-Null Cells Mol. Cell. Biol., April 1, 2002; 22(7): 2204 - 2219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ozen, D. Giri, F. Ropiquet, A. Mansukhani, and M. Ittmann Role of Fibroblast Growth Factor Receptor Signaling in Prostate Cancer Cell Survival J Natl Cancer Inst, December 5, 2001; 93(23): 1783 - 1790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Madewell, S. Griffey, J. Walls, and R. Gandour-Edwards Reduced Expression of Cyclin-dependent Kinase Inhibitor p27Kip1 in Feline Lymphoma Vet. Pathol., November 1, 2001; 38(6): 698 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-H. Park, J. Y. Seol, T.-Y. Kim, C.-G. Yoo, Y. W. Kim, S. K. Han, Y.-S. Shim, and C.-T. Lee An Adenovirus Expressing Mutant p27 Showed More Potent Antitumor Effects Than Adenovirus-p27 Wild Type Cancer Res., August 1, 2001; 61(16): 6163 - 6169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Said, R. C. B. Moraes, U. Singh, F. S. Kittrell, and D. Medina Cyclin-dependent Kinase (cdk) Inhibitors/cdk4/cdk2 Complexes in Early Stages of Mouse Mammary Preneoplasia Cell Growth Differ., June 1, 2001; 12(6): 285 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. I. Shapiro, J. G. Supko, A. Patterson, C. Lynch, J. Lucca, P. F. Zacarola, A. Muzikansky, J. J. Wright, T. J. Lynch Jr., and B. J. Rollins A Phase II Trial of the Cyclin-dependent Kinase Inhibitor Flavopiridol in Patients with Previously Untreated Stage IV Non-Small Cell Lung Cancer Clin. Cancer Res., June 1, 2001; 7(6): 1590 - 1599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Esposito, S. Pucciarelli, R. Alaggio, L. Giacomelli, E. Marchiori, G. A. Iaderosa, M. L. Friso, P. Toppan, L. Chieco-Bianchi, and M. Lise p27kip1 Expression Is Associated With Tumor Response to Preoperative Chemoradiotherapy in Rectal Cancer Ann. Surg. Oncol., May 1, 2001; 8(4): 311 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jeay, G. E. Sonenshein, P. A. Kelly, M.-C. Postel-Vinay, and E. Baixeras Growth Hormone Exerts Antiapoptotic and Proliferative Effects through Two Different Pathways Involving Nuclear Factor-{{kappa}}B and Phosphatidylinositol 3-Kinase Endocrinology, January 1, 2001; 142(1): 147 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Masciullo, G. Ferrandina, B. Pucci, F. Fanfani, S. Lovergine, J. Palazzo, G. Zannoni, S. Mancuso, G. Scambia, and A. Giordano p27Kip1 Expression Is Associated with Clinical Outcome in Advanced Epithelial Ovarian Cancer: Multivariate Analysis Clin. Cancer Res., December 1, 2000; 6(12): 4816 - 4822. [Abstract] [Full Text]
|
|
|
|
|
|
F. Hommura, H. Dosaka-Akita, T. Mishina, M. Nishi, T. Kojima, H. Hiroumi, S. Ogura, M. Shimizu, H. Katoh, and Y. Kawakami Prognostic Significance of p27KIP1 Protein and Ki-67 Growth Fraction in Non-small Cell Lung Cancers Clin. Cancer Res., October 1, 2000; 6(10): 4073 - 4081. [Abstract] [Full Text]
|
|
|
|
|
|
A. P. Albino, G. Juan, F. Traganos, L. Reinhart, J. Connolly, D. P. Rose, and Z. Darzynkiewicz Cell Cycle Arrest and Apoptosis of Melanoma Cells by Docosahexaenoic Acid: Association with Decreased pRb Phosphorylation Cancer Res., August 1, 2000; 60(15): 4139 - 4145. [Abstract] [Full Text]
|
|
|
|
|
|
D. Busse, R. S. Doughty, T. T. Ramsey, W. E. Russell, J. O. Price, W. M. Flanagan, L. K. Shawver, and C. L. Arteaga Reversible G1 Arrest Induced by Inhibition of the Epidermal Growth Factor Receptor Tyrosine Kinase Requires Up-regulation of p27KIP1 Independent of MAPK Activity J. Biol. Chem., March 15, 2000; 275(10): 6987 - 6995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Senderowicz and E. A. Sausville Preclinical and Clinical Development of Cyclin-Dependent Kinase Modulators J Natl Cancer Inst, March 1, 2000; 92(5): 376 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kudo, T. Takata, I. Ogawa, T. Kaneda, S. Sato, T. Takekoshi, M. Zhao, M. Miyauchi, and H. Nikai p27Kip1 Accumulation by Inhibition of Proteasome Function Induces Apoptosis in Oral Squamous Cell Carcinoma Cells Clin. Cancer Res., March 1, 2000; 6(3): 916 - 923. [Abstract] [Full Text]
|
|
|
|
|
|
M. Wu, R. E. Bellas, J. Shen, W. Yang, and G. E. Sonenshein Increased p27Kip1 Cyclin-Dependent Kinase Inhibitor Gene Expression Following Anti-IgM Treatment Promotes Apoptosis of WEHI 231 B Cells J. Immunol., December 15, 1999; 163(12): 6530 - 6535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, S. Lu, E. Miyagi, R. Katoh, and A. Kawaoi Thyrotropin Prevents Apoptosis by Promoting Cell Adhesion and Cell Cycle Progression in FRTL-5 Cells Endocrinology, December 1, 1999; 140(12): 5962 - 5970. [Abstract] [Full Text]
|
|
|
|
 |
|
 H. Oka, L. Jin, E. Kulig, B. W. Scheithauer, and R. V. Lloyd Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Transforming Growth Factor-{beta}1-Induced Apoptosis in a Human Pituitary Adenoma Cell Line Am. J. Pathol., December 1, 1999; 155(6): 1893 - 1900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Gilmour, M. Birchler, M. K. Smith, K. Rayca, and J. Mostochuk Effect of Elevated Levels of Ornithine Decarboxylase on Cell Cycle Progression in Skin Cell Growth Differ., November 1, 1999; 10(11): 739 - 748. [Abstract] [Full Text]
|
|
|
|
|
|
M. Baekelandt, R. Holm, C. G. Trope, J. M. Nesland, and G. B. Kristensen Lack of Independent Prognostic Significance of p21 and p27 Expression in Advanced Ovarian Cancer: An Immunohistochemical Study Clin. Cancer Res., October 1, 1999; 5(10): 2848 - 2853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. I. Shapiro, D. A. Koestner, C. B. Matranga, and B. J. Rollins Flavopiridol Induces Cell Cycle Arrest and p53-independent Apoptosis in Non-Small Cell Lung Cancer Cell Lines Clin. Cancer Res., October 1, 1999; 5(10): 2925 - 2938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. O'Rourke, G. C. Newbound, J. A. Hutt, and J. DeWille CCAAT/Enhancer-binding Protein delta Regulates Mammary Epithelial Cell G0 Growth Arrest and Apoptosis J. Biol. Chem., June 4, 1999; 274(23): 16582 - 16589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Santoni-Rugiu, M. R. Jensen, V. M. Factor, and S. S. Thorgeirsson Acceleration of c-myc-Induced Hepatocarcinogenesis by Co-Expression of Transforming Growth Factor (TGF)-{alpha} in Transgenic Mice Is Associated with TGF-ß1 Signaling Disruption Am. J. Pathol., June 1, 1999; 154(6): 1693 - 1700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Montagnoli, F. Fiore, E. Eytan, A. C. Carrano, G. F. Draetta, A. Hershko, and M. Pagano Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation Genes & Dev., May 1, 1999; 13(9): 1181 - 1189. [Abstract] [Full Text]
|
|
|
|
|
|
R. V. Lloyd, L. A. Erickson, L. Jin, E. Kulig, X. Qian, J. C. Cheville, and B. W. Scheithauer p27kip1: A Multifunctional Cyclin-Dependent Kinase Inhibitor with Prognostic Significance in Human Cancers Am. J. Pathol., February 1, 1999; 154(2): 313 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. V. Thomas, K. Szigeti, M. Murphy, G. Draetta, M. Pagano, and M. Loda Down-Regulation of p27 Is Associated with Development of Colorectal Adenocarcinoma Metastases Am. J. Pathol., September 1, 1998; 153(3): 681 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ma, D. Papermaster, and C. L. Cepko A unique pattern of photoreceptor degeneration in cyclin D1 mutant mice PNAS, August 18, 1998; 95(17): 9938 - 9943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Erlanson, C. Portin, B. Linderholm, J. Lindh, G. Roos, and G. Landberg Expression of Cyclin E and the Cyclin-Dependent Kinase Inhibitor p27 in Malignant Lymphomas---Prognostic Implications Blood, August 1, 1998; 92(3): 770 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hoshino, S. Tanimura, K. Watanabe, T. Kataoka, and M. Kohno Blockade of the Extracellular Signal-regulated Kinase Pathway Induces Marked G1 Cell Cycle Arrest and Apoptosis in Tumor Cells in Which the Pathway Is Constitutively Activated. UP-REGULATION OF p27Kip1 J. Biol. Chem., January 19, 2001; 276(4): 2686 - 2692. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
