| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
Departments of Thoracic/Head and Neck Medical Oncology [N. S., H. Y. L., W. K. H., J. M. K.] and Thoracic and Cardiovascular Surgery [G. L. W.], University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
Retinoids have demonstrated activity in the chemoprevention of aerodigestive tract cancer. Potentially contributing to their lung cancer chemopreventive effects, retinoids inhibit the growth of human bronchial epithelial (HBE) cells. We observed previously that all-trans retinoic acid (t-RA) arrests the growth of HBE cells in the G0 phase of the cell cycle through activation of retinoic acid receptor-dependent pathways, which enhances the association of E2F-4 with retinoblastoma protein family members, converting E2F into a transcriptional suppressor. In this study, we examined the mechanism by which t-RA blocks cell cycle progression in HBE cells and the possibility that this signaling event is blocked in non-small cell lung cancer (NSCLC) cells that are refractory to the growth inhibitory effects of t-RA. t-RA suppressed the expression and activity of cyclin D1, cyclin E, and cyclin-dependent kinases (CDK)-2 and CDK-4, increased expression of the CDK inhibitor p27, and shifted the retinoblastoma protein to a hypophosphorylated form. Posttranslational mechanisms contributed to the changes in CDK-2, CDK-4, and p27 levels, which, in the case of CDK-4, involved the ubiquitin-proteasome pathway. In contrast, despite retinoic acid receptor transcriptional activation, these signaling events did not occur in a NSCLC cell line that is refractory to growth inhibition by t-RA. These findings provide the first evidence that t-RA activates degradation of CDK-4 through the ubiquitin-proteasome pathway, a novel mechanism by which t-RA causes HBE cells to exit the cell cycle, and blockade of these signaling events may contribute to the development of retinoid resistance in NSCLC cells.
This article has been cited by other articles:
|
|
 |
|
  B. Trojanowicz, A. Winkler, K. Hammje, Z. Chen, C. Sekulla, D. Glanz, C. Schmutzler, B. Mentrup, S. Hombach-Klonisch, T. Klonisch, et al. Retinoic acid-mediated down-regulation of ENO1/MBP-1 gene products caused decreased invasiveness of the follicular thyroid carcinoma cell lines J. Mol. Endocrinol., March 1, 2009; 42(3): 249 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ravikumar, G. Perez-Liz, L. Del Vale, D. R. Soprano, and K. J. Soprano Insulin Receptor Substrate-1 Is an Important Mediator of Ovarian Cancer Cell Growth Suppression by All-trans Retinoic Acid Cancer Res., October 1, 2007; 67(19): 9266 - 9275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Kim, H. Lee, H. Kim, Y. M. Shim, J. Han, J. Park, and D.-H. Kim Promoter Methylation of Retinoic Acid Receptor Beta 2 and the Development of Second Primary Lung Cancers in Non-Small-Cell Lung Cancer J. Clin. Oncol., September 1, 2004; 22(17): 3443 - 3450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H. Dragnev, I. Pitha-Rowe, Y. Ma, W. J. Petty, D. Sekula, B. Murphy, M. Rendi, N. Suh, N. B. Desai, M. B. Sporn, et al. Specific Chemopreventive Agents Trigger Proteasomal Degradation of G1 Cyclins: Implications for Combination Therapy Clin. Cancer Res., April 1, 2004; 10(7): 2570 - 2577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vuocolo, E. Purev, D. Zhang, J. Bartek, K. Hansen, D. R. Soprano, and K. J. Soprano Protein Phosphatase 2A Associates with Rb2/p130 and Mediates Retinoic Acid-induced Growth Suppression of Ovarian Carcinoma Cells J. Biol. Chem., October 24, 2003; 278(43): 41881 - 41889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ratschiller, J. Heighway, M. Gugger, A. Kappeler, F. Pirnia, R.A. Schmid, M.M. Borner, and D.C. Betticher Cyclin D1 Overexpression in Bronchial Epithelia of Patients With Lung Cancer Is Associated With Smoking and Predicts Survival J. Clin. Oncol., June 1, 2003; 21(11): 2085 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Crowe, R. Kim, and R. A.S. Chandraratna Retinoic Acid Differentially Regulates Cancer Cell Proliferation via Dose-Dependent Modulation of the Mitogen-Activated Protein Kinase Pathway Mol. Cancer Res., May 1, 2003; 1(7): 532 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Pereira, Y. Li, W. T. Gunning, P. M. Kramer, F. Al-Yaqoub, R. A. Lubet, V. E. Steele, E. Szabo, and L. Tao Prevention of mouse lung tumors by budesonide and its modulation of biomarkers Carcinogenesis, July 1, 2002; 23(7): 1185 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Witschi, I. Espiritu, M. Suffia, and K. E. Pinkerton Expression of cyclin D1/2 in the lungs of strain A/J mice fed chemopreventive agents Carcinogenesis, February 1, 2002; 23(2): 289 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Dow, J. Hendley, A. Pirkmaier, E. A. Musgrove, and D. Germain Retinoic Acid-mediated Growth Arrest Requires Ubiquitylation and Degradation of the F-box Protein Skp2 J. Biol. Chem., November 30, 2001; 276(49): 45945 - 45951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Papadimitrakopoulou, J. Izzo, L. Mao, J. Keck, D. Hamilton, D. M. Shin, A. El-Naggar, P. den Hollander, D. Liu, W. N. Hittelman, et al. Cyclin D1 and p16 Alterations in Advanced Premalignant Lesions of the Upper Aerodigestive Tract: Role in Response to Chemoprevention and Cancer Development Clin. Cancer Res., October 1, 2001; 7(10): 3127 - 3134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Miano and B. C. Berk Retinoids: New Insight Into Smooth Muscle Cell Growth Inhibition Arterioscler Thromb Vasc Biol, May 1, 2001; 21(5): 724 - 726. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sueoka, H.-Y. Lee, G. L. Walsh, B. Fang, L. Ji, J. A. Roth, R. LaPushin, W. K. Hong, P. Cohen, and J. M. Kurie Insulin-Like Growth Factor Binding Protein-6 Inhibits the Growth of Human Bronchial Epithelial Cells and Increases in Abundance with All-trans-Retinoic Acid Treatment Am. J. Respir. Cell Mol. Biol., September 1, 2000; 23(3): 297 - 303. [Abstract] [Full Text]
|
|
| 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 |
