Cancer Research Annual Meeting 2010 Protein Translation and Cancer
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
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zeng, X.
Right arrow Articles by Glazer, R. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zeng, X.
Right arrow Articles by Glazer, R. I.
[Cancer Research 62, 3538-3543, June 15, 2002]
© 2002 American Association for Cancer Research

Tumor Biology

Transformation of Mammary Epithelial Cells by 3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) Is Associated with the Induction of Protein Kinase C{alpha}1

Xiao Zeng, Hangmin Xu and Robert I. Glazer2

Departments of Pharmacology and Oncology, Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC 20007

3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a mediator of multiple signaling pathways coupled to growth factor receptor activation in human cancers. To evaluate the role of PDK1 in mammary gland oncogenesis, COMMA-1D mouse mammary epithelial cells were retrovirally transduced with PDK1, and transformation was measured by anchorage-independent growth in soft agar. PDK1-expressing cells exhibited a high degree of transformation that was associated with the activation of Akt1 and an elevation of protein kinase C{alpha} (PKC{alpha}) expression. Cells overexpressing Akt1 did not exhibit anchorage-independent growth, whereas PKC{alpha} overexpression produced significant transformation, although to a lesser extent compared with PDK1. Coexpression of Akt1 and PKC{alpha} led to a more than additive effect on transformation activity. Isografts of either PDK1- or PKC{alpha}-expressing cells but not Akt1-expressing cells in syngeneic mice led to formation of poorly differentiated mammary carcinomas. PDK1 was highly expressed in a majority of human breast cancer cell lines. These results suggest that activation of PDK1 can lead to mammary tumorigenesis, in part through PKC{alpha}, and that PDK1 expression may be an important target in human breast cancer.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
M. Maurer, T. Su, L. H. Saal, S. Koujak, B. D. Hopkins, C. R. Barkley, J. Wu, S. Nandula, B. Dutta, Y. Xie, et al.
3-Phosphoinositide-Dependent Kinase 1 Potentiates Upstream Lesions on the Phosphatidylinositol 3-Kinase Pathway in Breast Carcinoma
Cancer Res., August 1, 2009; 69(15): 6299 - 6306.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
Y. Liu, J. Wang, M. Wu, W. Wan, R. Sun, D. Yang, X. Sun, D. Ma, G. Ying, and N. Zhang
Down-Regulation of 3-Phosphoinositide-Dependent Protein Kinase-1 Levels Inhibits Migration and Experimental Metastasis of Human Breast Cancer Cells
Mol. Cancer Res., June 1, 2009; 7(6): 944 - 954.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Yin, H. Yuan, X. Zeng, L. Kopelovich, and R. I. Glazer
Inhibition of Peroxisome Proliferator-Activated Receptor {gamma} Increases Estrogen Receptor-Dependent Tumor Specification
Cancer Res., January 15, 2009; 69(2): 687 - 694.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
X.-Y. Wang, Y. Yin, H. Yuan, T. Sakamaki, H. Okano, and R. I. Glazer
Musashi1 Modulates Mammary Progenitor Cell Expansion through Proliferin-Mediated Activation of the Wnt and Notch Pathways
Mol. Cell. Biol., June 1, 2008; 28(11): 3589 - 3599.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. Pearn, J. Fisher, A. K. Burnett, and R. L. Darley
The role of PKC and PDK1 in monocyte lineage specification by Ras
Blood, May 15, 2007; 109(10): 4461 - 4469.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. Lehnes, A. D. Winder, C. Alfonso, N. Kasid, M. Simoneaux, H. Summe, E. Morgan, M. C. Iann, J. Duncan, M. Eagan, et al.
The Effect of Estradiol on in Vivo Tumorigenesis Is Modulated by the Human Epidermal Growth Factor Receptor 2/Phosphatidylinositol 3-Kinase/Akt1 Pathway
Endocrinology, March 1, 2007; 148(3): 1171 - 1180.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
K. Liang, Y. Lu, X. Li, X. Zeng, R. I. Glazer, G. B. Mills, and Z. Fan
Differential Roles of Phosphoinositide-Dependent Protein Kinase-1 and Akt1 Expression and Phosphorylation in Breast Cancer Cell Resistance to Paclitaxel, Doxorubicin, and Gemcitabine
Mol. Pharmacol., September 1, 2006; 70(3): 1045 - 1052.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
Y. Yin, H. Yuan, C. Wang, N. Pattabiraman, M. Rao, R. G. Pestell, and R. I. Glazer
3-Phosphoinositide-Dependent Protein Kinase-1 Activates the Peroxisome Proliferator-Activated Receptor-{gamma} and Promotes Adipocyte Differentiation
Mol. Endocrinol., February 1, 2006; 20(2): 268 - 278.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Tanaka, N. Fujita, and T. Tsuruo
3-Phosphoinositide-dependent Protein Kinase-1-mediated I{kappa}B Kinase {beta} (IKKB) Phosphorylation Activates NF-{kappa}B Signaling
J. Biol. Chem., December 9, 2005; 280(49): 40965 - 40973.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Hara, Y. Saito, T. Hirai, K. Nakamura, K. Nakao, M. Katsuki, and K. Chida
Deficiency of Protein Kinase C{alpha} in Mice Results in Impairment of Epidermal Hyperplasia and Enhancement of Tumor Formation in Two-Stage Skin Carcinogenesis
Cancer Res., August 15, 2005; 65(16): 7356 - 7362.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Yin, R. G. Russell, L. E. Dettin, R. Bai, Z.-L. Wei, A. P. Kozikowski, L. Kopleovich, and R. I. Glazer
Peroxisome Proliferator-Activated Receptor {delta} and {gamma} Agonists Differentially Alter Tumor Differentiation and Progression during Mammary Carcinogenesis
Cancer Res., May 1, 2005; 65(9): 3950 - 3957.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Y. Niv, H. Rubin, J. Cohen, L. Tsirulnikov, T. Licht, A. Peretzman-Shemer, E. Cna'an, A. Tartakovsky, I. Stein, S. Albeck, et al.
Sequence-based Design of Kinase Inhibitors Applicable for Therapeutics and Target Identification
J. Biol. Chem., January 9, 2004; 279(2): 1242 - 1255.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. A. Lim, C. K. Kikani, M. J. Wick, and L. Q. Dong
Nuclear translocation of 3'-phosphoinositide-dependent protein kinase 1 (PDK-1): A potential regulatory mechanism for PDK-1 function
PNAS, November 25, 2003; 100(24): 14006 - 14011.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Z. Xie, X. Zeng, T. Waldman, and R. I. Glazer
Transformation of Mammary Epithelial Cells by 3-Phosphoinositide- dependent Protein Kinase-1 Activates {beta}-Catenin and c-Myc, and Down-Regulates Caveolin-1
Cancer Res., September 1, 2003; 63(17): 5370 - 5375.
[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
Copyright © 2002 by the American Association for Cancer Research.