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[Cancer Research 63, 196-206, January 2003]
© 2003 American Association for Cancer Research

Tumor Biology

Overexpression of AKT2/Protein Kinase Bß Leads to Up-Regulation of ß1 Integrins, Increased Invasion, and Metastasis of Human Breast and Ovarian Cancer Cells1

M. Jane Arboleda2, John F. Lyons, Fairooz F. Kabbinavar, Mark R. Bray, Bryan E. Snow, Raul Ayala, Mordechai Danino, Beth Y. Karlan and Dennis J. Slamon

Department of Medicine, Division of Hematology and Oncology, University of California-Los Angeles (UCLA), UCLA School of Medicine, Los Angeles, California 90095 [M. J. A., F. F. K., R. A., M. D., D. J. S.]; ONYX Pharmaceuticals, Richmond, California 94806 [J. F. L.]; Amgen Research Institute, Toronto, Ontario, M5G 2C1 Canada [M. R. B., B. E. S.]; and Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California 90095 [B. Y. K.]

To determine how AKT2 might contribute to tumor cell progression, a full-length, wild-type, human AKT2/protein kinase B (PKB)ß cDNA was transfected into a panel of eight human breast and ovarian cancer cells. AKT2 transfectants demonstrated increased adhesion and invasion through collagen IV because of up-regulation of ß1 integrins. In addition, AKT2 cells were more metastatic than control cells in vivo. Increased invasion by AKT2 was blocked by preincubation with an anti-ß1 integrin function blocking antibody, exposure to wortmannin, and by expression of phosphatase and tensin homologue tumor suppressor (PTEN). Confocal microscopy performed on transfected human breast cancer cells showed that unlike AKT1, AKT2 protein predominantly localized adjacent to the collagen IV matrix during cellular attachment. Overexpression of AKT2, but not AKT1 or AKT3, was sufficient to duplicate the invasive effects of phosphoinositide 3-OH kinase (PI3-K) transfected in breast cancer cells. Furthermore, expression of kinase dead AKT2(181 amino acid methionine [M]), and not kinase dead AKT1(179M) or AKT3(177M), was capable of blocking invasion induced by either human epidermal growth factor receptor-2 (HER-2) overexpression or by activation of PI3-K. Taken together, these data indicate that AKT2 mediates PI3-K-dependent effects on adhesion, motility, invasion, and metastasis in vivo.




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Home page
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J. Cell Sci., December 15, 2005; 118(24): 5675 - 5678.
[Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

Home page
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Carcinogenesis, November 1, 2004; 25(11): 2053 - 2059.
[Abstract] [Full Text] [PDF]

Home page
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Mol. Cell. Biol., June 15, 2004; 24(12): 5565 - 5576.
[Abstract] [Full Text] [PDF]

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Cancer Res., June 15, 2004; 64(12): 4190 - 4196.
[Abstract] [Full Text] [PDF]

Home page
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Cancer Res., May 15, 2004; 64(10): 3500 - 3507.
[Abstract] [Full Text] [PDF]

Home page
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Clin. Cancer Res., May 1, 2004; 10(9): 3216 - 3224.
[Abstract] [Full Text] [PDF]

Home page
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Mol. Cell. Biol., April 15, 2004; 24(8): 3526 - 3535.
[Abstract] [Full Text] [PDF]

Home page
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Endocrinology, April 1, 2004; 145(4): 2014 - 2022.
[Abstract] [Full Text] [PDF]

Home page
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Cancer Res., October 15, 2003; 63(20): 6697 - 6706.
[Abstract] [Full Text] [PDF]

Home page
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