Cancer Research 09 AM Call for Abstracts
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 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 Tanno, S.
Right arrow Articles by Testa, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tanno, S.
Right arrow Articles by Testa, J. R.
[Cancer Research 61, 589-593, January 15, 2001]
© 2001 American Association for Cancer Research

Tumor Biology

AKT Activation Up-Regulates Insulin-like Growth Factor I Receptor Expression and Promotes Invasiveness of Human Pancreatic Cancer Cells1

Satoshi Tanno, Sachie Tanno, Yasuhiro Mitsuuchi, Deborah A. Altomare, Guang-Hui Xiao and Joseph R. Testa2

Human Genetics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111

Insulin-like growth factor I receptor (IGF-IR) is frequently overexpressed in several types of human malignancy and is associated with invasion and metastasis of tumor cells. Recently, IGF-IR expression was reported to be up-regulated in the human pancreatic cancer cell line PANC-1 when cells were stably transfected with active Src. The downstream targets of Src that lead to the up-regulation of IGF-IR expression were previously unknown. We demonstrate here that AKT regulates IGF-IR expression in PANC-1 and AsPC-1 cells. Cells transfected with active Src exhibited significantly more IGF-IR protein compared with vector-transfected cells. Overexpression of wild-type or constitutively active AKT (i.e., AKT1 or AKT2) also resulted in elevated IGF-IR expression. IGF-IR protein levels were higher in cells transfected with constitutively active AKT than in cells transfected with active Src. In vitro kinase assays showed that AKT kinases are activated by active Src and inhibited by dominant negative Src or the tumor suppressor PTEN. Furthermore, AKT-induced IGF-IR expression was down-regulated by dominantnegative Src or PTEN. In addition, cells transfected with activated AKT in the presence of IGF-I were shown to have enhanced invasiveness compared with control cells. These data provide evidence for a link between AKT signaling and the regulation of IGF-IR expression and demonstrate that active AKT promotes the invasiveness of pancreatic cancer cells through the up-regulation of IGF-IR expression.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
E. Castro-Rivera, S. Ran, R. A. Brekken, and J. D. Minna
Semaphorin 3B Inhibits the Phosphatidylinositol 3-Kinase/Akt Pathway through Neuropilin-1 in Lung and Breast Cancer Cells
Cancer Res., October 15, 2008; 68(20): 8295 - 8303.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
M. Degtyarev, A. De Maziere, C. Orr, J. Lin, B. B. Lee, J. Y. Tien, W. W. Prior, S. van Dijk, H. Wu, D. C. Gray, et al.
Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents
J. Cell Biol., October 6, 2008; 183(1): 101 - 116.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. G. Hollier, J. A. Kricker, D. R. Van Lonkhuyzen, D. I. Leavesley, and Z. Upton
Substrate-Bound Insulin-Like Growth Factor (IGF)-I-IGF Binding Protein-Vitronectin-Stimulated Breast Cell Migration Is Enhanced by Coactivation of the Phosphatidylinositide 3-Kinase/AKT Pathway by {alpha}v-Integrins and the IGF-I Receptor
Endocrinology, March 1, 2008; 149(3): 1075 - 1090.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Z. Cheng, W. Zhang, and L.-H. Wang
Regulation of Cancer Cell Survival, Migration, and Invasion by Twist: AKT2 Comes to Interplay
Cancer Res., February 15, 2008; 68(4): 957 - 960.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
M. Ye, D. Hu, L. Tu, X. Zhou, F. Lu, B. Wen, W. Wu, Y. Lin, Z. Zhou, and J. Qu
Involvement of PI3K/Akt Signaling Pathway in Hepatocyte Growth Factor-Induced Migration of Uveal Melanoma Cells
Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 497 - 504.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Z. Guan, X.-r. Wang, X.-f. Zhu, X.-f. Huang, J. Xu, L.-h. Wang, X.-b. Wan, Z.-j. Long, J.-n. Liu, G.-k. Feng, et al.
Aurora-A, a Negative Prognostic Marker, Increases Migration and Decreases Radiosensitivity in Cancer Cells
Cancer Res., November 1, 2007; 67(21): 10436 - 10444.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. M. Thomas, K. Toney, C. Fenoglio-Preiser, M. P. Revelo-Penafiel, S. R. Hingorani, D. A. Tuveson, S. E. Waltz, and A. M. Lowy
The RON Receptor Tyrosine Kinase Mediates Oncogenic Phenotypes in Pancreatic Cancer Cells and Is Increasingly Expressed during Pancreatic Cancer Progression
Cancer Res., July 1, 2007; 67(13): 6075 - 6082.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
X. Ju, S. Katiyar, C. Wang, M. Liu, X. Jiao, S. Li, J. Zhou, J. Turner, M. P. Lisanti, R. G. Russell, et al.
Akt1 governs breast cancer progression in vivo
PNAS, May 1, 2007; 104(18): 7438 - 7443.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. Jin, C. Yun, A. Hobbie, M. J. Martin, P. H.B. Sorensen, and S.-J. Kim
Cellular Transformation and Activation of the Phosphoinositide-3-Kinase-Akt Cascade by the ETV6-NTRK3 Chimeric Tyrosine Kinase Requires c-Src
Cancer Res., April 1, 2007; 67(7): 3192 - 3200.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
P. C.K. Leung and J.-H. Choi
Endocrine signaling in ovarian surface epithelium and cancer
Hum. Reprod. Update, March 1, 2007; 13(2): 143 - 162.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. S. Douglas, A. G. Gianoukakis, S. Kamat, and T. J. Smith
Aberrant Expression of the Insulin-Like Growth Factor-1 Receptor by T Cells from Patients with Graves' Disease May Carry Functional Consequences for Disease Pathogenesis
J. Immunol., March 1, 2007; 178(5): 3281 - 3287.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. S. McCampbell, R. R. Broaddus, D. S. Loose, and P. J.A. Davies
Overexpression of the Insulin-Like Growth Factor I Receptor and Activation of the AKT Pathway in Hyperplastic Endometrium.
Clin. Cancer Res., November 1, 2006; 12(21): 6373 - 6378.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Toker and M. Yoeli-Lerner
Akt Signaling and Cancer: Surviving but not Moving On.
Cancer Res., April 15, 2006; 66(8): 3963 - 3966.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
T. Yamauchi, M. Sakurai, K. Abe, H. Takano, and Y. Sawa
Neuroprotective Effects of Activated Protein C Through Induction of Insulin-Like Growth Factor-1 (IGF-1), IGF-1 Receptor, and Its Downstream Signal Phosphorylated Serine-Threonine Kinase After Spinal Cord Ischemia in Rabbits
Stroke, April 1, 2006; 37(4): 1081 - 1086.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Liu, D. C. Radisky, C. M. Nelson, H. Zhang, J. E. Fata, R. A. Roth, and M. J. Bissell
Mechanism of Akt1 inhibition of breast cancer cell invasion reveals a protumorigenic role for TSC2.
PNAS, March 14, 2006; 103(11): 4134 - 4139.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
J Lim, J-H Kim, J-Y Paeng, M-J Kim, S-D Hong, J-I Lee, and S-P Hong
Prognostic value of activated Akt expression in oral squamous cell carcinoma
J. Clin. Pathol., November 1, 2005; 58(11): 1199 - 1205.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Bjorndahl, R. Cao, L. J. Nissen, S. Clasper, L. A. Johnson, Y. Xue, Z. Zhou, D. Jackson, A. Jon Hansen, and Y. Cao
Insulin-like growth factors 1 and 2 induce lymphangiogenesis in vivo
PNAS, October 25, 2005; 102(43): 15593 - 15598.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Asano, Y. Yao, S. Shin, J. McCubrey, J. L. Abbruzzese, and S. A.G. Reddy
Insulin Receptor Substrate Is a Mediator of Phosphoinositide 3-Kinase Activation in Quiescent Pancreatic Cancer Cells
Cancer Res., October 15, 2005; 65(20): 9164 - 9168.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. W. Bauer, W. Liu, F. Fan, E. R. Camp, A. Yang, R. J. Somcio, C. D. Bucana, J. Callahan, G. C. Parry, D. B. Evans, et al.
Targeting of Urokinase Plasminogen Activator Receptor in Human Pancreatic Carcinoma Cells Inhibits c-Met- and Insulin-like Growth Factor-I Receptor-Mediated Migration and Invasion and Orthotopic Tumor Growth in Mice
Cancer Res., September 1, 2005; 65(17): 7775 - 7781.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
Y Min, Y Adachi, H Yamamoto, A Imsumran, Y Arimura, T Endo, Y Hinoda, C-T Lee, S Nadaf, D P Carbone, et al.
Insulin-like growth factor I receptor blockade enhances chemotherapy and radiation responses and inhibits tumour growth in human gastric cancer xenografts
Gut, May 1, 2005; 54(5): 591 - 600.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
I. Shin, S. Kim, H. Song, H.-R. C. Kim, and A. Moon
H-Ras-specific Activation of Rac-MKK3/6-p38 Pathway: ITS CRITICAL ROLE IN INVASION AND MIGRATION OF BREAST EPITHELIAL CELLS
J. Biol. Chem., April 15, 2005; 280(15): 14675 - 14683.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Nosho, H. Yamamoto, H. Taniguchi, Y. Adachi, Y. Yoshida, Y. Arimura, T. Endo, Y. Hinoda, and K. Imai
Interplay of Insulin-Like Growth Factor-II, Insulin-Like Growth Factor-I, Insulin-Like Growth Factor-I Receptor, COX-2, and Matrix Metalloproteinase-7, Play Key Roles in the Early Stage of Colorectal Carcinogenesis
Clin. Cancer Res., December 1, 2004; 10(23): 7950 - 7957.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
B. R. Balsara, J. Pei, Y. Mitsuuchi, R. Page, A. Klein-Szanto, H. Wang, M. Unger, and J. R. Testa
Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions
Carcinogenesis, November 1, 2004; 25(11): 2053 - 2059.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Tanno, N. Yanagawa, A. Habiro, K. Koizumi, Y. Nakano, M. Osanai, Y. Mizukami, T. Okumura, J. R. Testa, and Y. Kohgo
Serine/Threonine Kinase AKT Is Frequently Activated in Human Bile Duct Cancer and Is Associated with Increased Radioresistance
Cancer Res., May 15, 2004; 64(10): 3486 - 3490.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Suzuki, J. Lu, G.-i. Kusakai, A. Kishimoto, T. Ogura, and H. Esumi
ARK5 Is a Tumor Invasion-Associated Factor Downstream of Akt Signaling
Mol. Cell. Biol., April 15, 2004; 24(8): 3526 - 3535.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Tanaka, H. Kobayashi, M. Suzuki, N. Kanayama, and T. Terao
Transforming Growth Factor-{beta}1-dependent Urokinase Up-regulation and Promotion of Invasion Are Involved in Src-MAPK-dependent Signaling in Human Ovarian Cancer Cells
J. Biol. Chem., March 5, 2004; 279(10): 8567 - 8576.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Yasumaru, S. Tsuji, M. Tsujii, T. Irie, M. Komori, A. Kimura, T. Nishida, Y. Kakiuchi, N. Kawai, H. Murata, et al.
Inhibition of Angiotensin II Activity Enhanced the Antitumor Effect of Cyclooxygenase-2 Inhibitors via Insulin-Like Growth Factor I Receptor Pathway
Cancer Res., October 15, 2003; 63(20): 6726 - 6734.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Min, Y. Adachi, H. Yamamoto, H. Ito, F. Itoh, C.-T. Lee, S. Nadaf, D. P. Carbone, and K. Imai
Genetic Blockade of the Insulin-like Growth Factor-I Receptor: A Promising Strategy for Human Pancreatic Cancer
Cancer Res., October 1, 2003; 63(19): 6432 - 6441.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
G. Zhang, B. He, and G. F. Weber
Growth Factor Signaling Induces Metastasis Genes in Transformed Cells: Molecular Connection between Akt Kinase and Osteopontin in Breast Cancer
Mol. Cell. Biol., September 15, 2003; 23(18): 6507 - 6519.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
O. Stoeltzing, W. Liu, N. Reinmuth, F. Fan, A. A. Parikh, C. D. Bucana, D. B. Evans, G. L. Semenza, and L. M. Ellis
Regulation of Hypoxia-Inducible Factor-1{alpha}, Vascular Endothelial Growth Factor, and Angiogenesis by an Insulin-Like Growth Factor-I Receptor Autocrine Loop in Human Pancreatic Cancer
Am. J. Pathol., September 1, 2003; 163(3): 1001 - 1011.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. J. Grille, A. Bellacosa, J. Upson, A. J. Klein-Szanto, F. van Roy, W. Lee-Kwon, M. Donowitz, P. N. Tsichlis, and L. Larue
The Protein Kinase Akt Induces Epithelial Mesenchymal Transition and Promotes Enhanced Motility and Invasiveness of Squamous Cell Carcinoma Lines
Cancer Res., May 1, 2003; 63(9): 2172 - 2178.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
K. M. Woods Ignatoski, D. L. Livant, S. Markwart, N. K. Grewal, and S. P. Ethier
The Role of Phosphatidylinositol 3'-Kinase and Its Downstream Signals in erbB-2-Mediated Transformation
Mol. Cancer Res., May 1, 2003; 1(7): 551 - 560.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
S. Marino, P. Krimpenfort, C. Leung, H. A. G. M. van der Korput, J. Trapman, I. Camenisch, A. Berns, and S. Brandner
PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum
Development, March 9, 2003; 129(14): 3513 - 3522.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. J. Arboleda, J. F. Lyons, F. F. Kabbinavar, M. R. Bray, B. E. Snow, R. Ayala, M. Danino, B. Y. Karlan, and D. J. Slamon
Overexpression of AKT2/Protein Kinase B{beta} Leads to Up-Regulation of {beta}1 Integrins, Increased Invasion, and Metastasis of Human Breast and Ovarian Cancer Cells
Cancer Res., January 1, 2003; 63(1): 196 - 206.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Nakanishi, M. Sakamoto, J. Yasuda, M. Takamura, N. Fujita, T. Tsuruo, S. Todo, and S. Hirohashi
Critical Involvement of the Phosphatidylinositol 3-Kinase/Akt Pathway in Anchorage-independent Growth and Hematogeneous Intrahepatic Metastasis of Liver Cancer
Cancer Res., May 1, 2002; 62(10): 2971 - 2975.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B.-K. Park, X. Zeng, and R. I. Glazer
Akt1 Induces Extracellular Matrix Invasion and Matrix Metalloproteinase-2 Activity in Mouse Mammary Epithelial Cells
Cancer Res., October 1, 2001; 61(20): 7647 - 7653.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. R. Testa and A. Bellacosa
AKT plays a central role in tumorigenesis
PNAS, September 25, 2001; 98(20): 10983 - 10985.
[Full Text] [PDF]

Home page
 FASEB J.Home page
D. KIM, S. KIM, H. KOH, S.-O. YOON, A.-S. CHUNG, K. S. CHO, and J. CHUNG
Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production
FASEB J, September 1, 2001; 15(11): 1953 - 1962.
[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 © 2001 by the American Association for Cancer Research.