| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cancer Research Campaign Beatson Laboratories, University of Glasgow, Department of Medical Oncology, and Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, United Kingdom [S. L., A. J. S., A. B.]; Howard Hughes Medical Institute, Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105 [D. E. Q., C. J. S.]; and Imperial Cancer Research Fund, Laboratory of Molecular Oncology, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom [D. P., G. P.]
p16INK4a and p15INK4b are cell cycle regulators that specifically bind to and inhibit the cyclin D-dependent kinases, cdk4 and cdk6. Because these genes undergo frequent deletions and/or mutations in various human cancers, we examined the status and expression of the cognate mouse cdk inhibitors in a panel of 29 cell lines, as well as in 12 primary tumors, representing different stages of mouse skin carcinogenesis. Deletion of p16INK4a and/or p15INK4b was seen in 8 of 10 cell lines derived from spindle carcinomas, the most advanced stage of skin carcinogenesis. Five showed deletion of both genes, and three had independent deletions of p16INK4a or p15INK4b, but in those retaining p16INK4a, expression of the protein was not detected. By contrast, none of 19 more differentiated squamous cell lines exhibited such deletions. In several cases, primary tumor DNA was available, and two spindle tumors showed the same deletion pattern as observed in the corresponding cell lines. In apparent contrast, comparison of two clonally related squamous and spindle cell lines derived from a single carcinoma showed unusually high levels of p16INK4a and p15INK4b only in the invasive spindle cells. Therefore, deletion or altered regulation of p16INK4a and p15INK4b occur concomitantly with the loss of differentiation associated with the late spindle stage of tumor progression in mouse skin.
1 This work was supported by the Cancer Research Campaign, the United Kingdom Coordinating Committee for Cancer Research (to S. L.), and the West of Scotland Ladies Bowling Association Fellowship (to A. J. S.).
2 To whom requests for reprints should be addressed. Phone: 44-141-330 4886; Fax: 44-141-330 4063.
Received 8/ 1/95. Accepted 9/27/95.
This article has been cited by other articles:
|
|
 |
|
  R. Frum, M. Ramamoorthy, L. Mohanraj, S. Deb, and S. P. Deb MDM2 Controls the Timely Expression of Cyclin A to Regulate the Cell Cycle Mol. Cancer Res., August 1, 2009; 7(8): 1253 - 1267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Perez-Gomez, M. Villa-Morales, J. Santos, J. Fernandez-Piqueras, C. Gamallo, J. Dotor, C. Bernabeu, and M. Quintanilla A Role for Endoglin as a Suppressor of Malignancy during Mouse Skin Carcinogenesis Cancer Res., November 1, 2007; 67(21): 10268 - 10277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhang, R. Yao, J. Li, Y. Wang, C. W. Boone, R. A. Lubet, and M. You Induction of Invasive Mouse Skin Carcinomas in Transgenic Mice with Mutations in Both H-ras and p53 Mol. Cancer Res., October 1, 2005; 3(10): 563 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Deb Cell Cycle Regulatory Functions of the Human Oncoprotein MDM2 Mol. Cancer Res., December 1, 2003; 1(14): 1009 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Harada, H. Nakagawa, K. Oyama, M. Takaoka, C. D. Andl, B. Jacobmeier, A. von Werder, G. H. Enders, O. G. Opitz, and A. K. Rustgi Telomerase Induces Immortalization of Human Esophageal Keratinocytes Without p16INK4a Inactivation Mol. Cancer Res., August 1, 2003; 1(10): 729 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Macdiarmid, D. Stevenson, D. H. Campbell, and J. B. Wilson The latent membrane protein 1 of Epstein-Barr virus and loss of the INK4a locus: paradoxes resolve to cooperation in carcinogenesis in vivo Carcinogenesis, July 1, 2003; 24(7): 1209 - 1218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Zoumpourlis, S. Solakidi, A. Papathoma, and D. Papaevangeliou Alterations in signal transduction pathways implicated in tumour progression during multistage mouse skin carcinogenesis Carcinogenesis, July 1, 2003; 24(7): 1159 - 1165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Firestone and L. F. Bjeldanes Indole-3-Carbinol and 3-3'-Diindolylmethane Antiproliferative Signaling Pathways Control Cell-Cycle Gene Transcription in Human Breast Cancer Cells by Regulating Promoter-Sp1 Transcription Factor Interactions J. Nutr., July 1, 2003; 133(7): 2448S - 2455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Y. Kim, K.-H. Lee, S. Chang, C. Chung, H.-W. Lee, J. Yim, and T. K. Kim Oncogenic Potential of a Dominant Negative Mutant of Interferon Regulatory Factor 3 J. Biol. Chem., April 18, 2003; 278(17): 15272 - 15278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Govindarajan, X. Bai, C. Cohen, H. Zhong, S. Kilroy, G. Louis, M. Moses, and J. L Arbiser Malignant Transformation of Melanocytes to Melanoma by Constitutive Activation of Mitogen-activated Protein Kinase Kinase (MAPKK) Signaling J. Biol. Chem., March 7, 2003; 278(11): 9790 - 9795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Gibson, C. Y. Dai, H.-W. Lee, R. A. DePinho, M. S. Gee, W. M. F. Lee, E. E. Furth, C. Brensinger, and G. H. Enders Inhibition of Colon Tumor Progression and Angiogenesis by the Ink4a/Arf Locus Cancer Res., February 15, 2003; 63(4): 742 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W J Lemon, H Bernert, H Sun, Y Wang, and M You Identification of candidate lung cancer susceptibility genes in mouse using oligonucleotide arrays J. Med. Genet., September 1, 2002; 39(9): 644 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kato, S. Horiuchi, A. Takahashi, Y. Ueoka, T. Arima, T. Matsuda, H. Kato, J.-i. Nishida, Y. Nakabeppu, and N. Wake Contribution of Estrogen Receptor alpha to Oncogenic K-Ras-mediated NIH3T3 Cell Transformation and Its Implication for Escape from Senescence by Modulating the p53 Pathway J. Biol. Chem., March 22, 2002; 277(13): 11217 - 11224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Li, K. Dower, Y. Ma, Y. Tian, and T. L. Benjamin A tumor host range selection procedure identifies p150sal2 as a target of polyoma virus large T antigen PNAS, December 4, 2001; 98(25): 14619 - 14624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Paramio, C. Segrelles, S. Ruiz, J. Martin-Caballero, A. Page, J. Martinez, M. Serrano, and J. L. Jorcano The ink4a/arf Tumor Suppressors Cooperate with p21cip1/waf in the Processes of Mouse Epidermal Differentiation, Senescence, and Carcinogenesis J. Biol. Chem., November 16, 2001; 276(47): 44203 - 44211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. LaMontagne Jr., M. A. Moses, D. Wiederschain, S. Mahajan, J. Holden, H. Ghazizadeh, D. A. Frank, and J. L. Arbiser Inhibition of MAP Kinase Kinase Causes Morphological Reversion and Dissociation between Soft Agar Growth and in Vivo Tumorigenesis in Angiosarcoma Cells Am. J. Pathol., December 1, 2000; 157(6): 1937 - 1945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Serrano The INK4a/ARF locus in murine tumorigenesis Carcinogenesis, May 1, 2000; 21(5): 865 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Farwell, K. A. Shera, J. I. Koop, G. A. Bonnet, C. P. Matthews, G. W. Reuther, M. D. Coltrera, J. K. McDougall, and A. J. Klingelhutz Genetic and Epigenetic Changes in Human Epithelial Cells Immortalized by Telomerase Am. J. Pathol., May 1, 2000; 156(5): 1537 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Malumbres, I. Pérez De Castro, M. I. Hernández, M. Jiménez, T. Corral, and A. Pellicer Cellular Response to Oncogenic Ras Involves Induction of the Cdk4 and Cdk6 Inhibitor p15INK4b Mol. Cell. Biol., April 15, 2000; 20(8): 2915 - 2925. [Abstract] [Full Text]
|
|
|
|
|
|
A. Balmain and C. C.Harris Carcinogenesis in mouse and human cells: parallels and paradoxes Carcinogenesis, March 1, 2000; 21(3): 371 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zou, F. Cong, M. Coutts, G. Cattoretti, S. P. Goff, and K. Calame p53 Deficiency Increases Transformation by v-Abl and Rescues the Ability of a C-Terminally Truncated v-Abl Mutant To Induce Pre-B Lymphoma In Vivo Mol. Cell. Biol., January 15, 2000; 20(2): 628 - 633. [Abstract] [Full Text]
|
|
|
|
|
|
C. J. Kemp, K. Vo, and K. E. Gurley Resistance to skin tumorigenesis in DNAPK-deficient SCID mice is not due to immunodeficiency but results from hypersensitivity to TPA-induced apoptosis Carcinogenesis, November 1, 1999; 20(11): 2051 - 2056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. W. Lin, M. Barradas, J. C. Stone, L. van Aelst, M. Serrano, and S. W. Lowe Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling Genes & Dev., October 1, 1998; 12(19): 3008 - 3019. [Abstract] [Full Text]
|
|
|
|
|
|
W. Jiang, H. N. Ananthaswamy, H. K. Muller, A. Ouhtit, S. Bolshakov, S. E. Ullrich, A. K. El-Naggar, and M. L. Kripke UV irradiation augments lymphoid malignancies in mice with one functional copy of wild-type p53 PNAS, August 14, 2001; 98(17): 9790 - 9795. [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 |
