Cancer Research AACR Legacy Sign up for Cancer Research eTOC's
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 Zhu, T.
Right arrow Articles by Lobie, P. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhu, T.
Right arrow Articles by Lobie, P. E.
[Cancer Research 65, 317-324, January 1, 2005]
© 2005 American Association for Cancer Research

Endocrinology

Oncogenic Transformation of Human Mammary Epithelial Cells by Autocrine Human Growth Hormone

Tao Zhu1, B. Starling-Emerald3, Xin Zhang2, Kok-Onn Lee2, Peter D. Gluckman3, Hichem C. Mertani4 and Peter E. Lobie1,3

1 Institute of Molecular and Cell Biology and 2 Department of Medicine, National University of Singapore, Singapore, Republic of Singapore; 3 Liggins Institute and National Research Centre for Growth and Development, University of Auckland, Auckland, New Zealand; and 4 Centre National de la Recherche Scientifique UMR 5578, Physiologies Energetiques Cellulaires et Moléculaires, Université Claude Bernard, Lyon-1, France

Requests for reprints: Peter E. Lobie, Liggins Institute, University of Auckland, 2-6 Park Avenue, Private Bag 92019, Auckland, New Zealand. Phone: 64-9-3737599 ext. 82125; Fax: 64-9-3737497; E-mail; p.lobie{at}auckland.ac.nz.

The human growth hormone (hGH) gene is expressed in the normal human mammary epithelial cell and its expression increases concomitant with the acquisition of proliferative lesions. Herein we demonstrate that autocrine production of hGH in human mammary carcinoma cells dramatically enhances anchorage-independent growth in a Janus kinase 2–dependent manner. Forced expression of the hGH gene in immortalized human mammary epithelial cells increased proliferation, decreased apoptosis, altered the cellular morphology and resulted in oncogenic transformation. Autocrine hGH was therefore sufficient to support anchorage-independent growth of immortalized human mammary epithelial cells and tumor formation in vivo. Moreover, autocrine hGH disrupted normal mammary acinar architecture with luminal filling and deregulated proliferation in three-dimensional epithelial cell culture. Autocrine hGH utilized homeobox A1 to govern the transcriptional program required for autocrine hGH–stimulated oncogenic transformation of human mammary epithelial cells, including transcriptional up-regulation of c-Myc, cyclin D1, and Bcl-2. Forced expression of a single orthotopically expressed wild-type gene is therefore sufficient for oncogenic transformation of the immortalized human mammary epithelial cell.




This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
C. Clapp, S. Thebault, M. C. Jeziorski, and G. Martinez De La Escalera
Peptide Hormone Regulation of Angiogenesis
Physiol Rev, October 1, 2009; 89(4): 1177 - 1215.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. Amiry, X. Kong, N. Muniraj, N. Kannan, P. M. Grandison, J. Lin, Y. Yang, C. M. Vouyovitch, S. Borges, J. K. Perry, et al.
Trefoil Factor-1 (TFF1) Enhances Oncogenicity of Mammary Carcinoma Cells
Endocrinology, October 1, 2009; 150(10): 4473 - 4483.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. E. Brunet-Dunand, C. Vouyovitch, S. Araneda, V. Pandey, L. J.-P. Vidal, C. Print, H. C. Mertani, P. E. Lobie, and J. K. Perry
Autocrine Human Growth Hormone Promotes Tumor Angiogenesis in Mammary Carcinoma
Endocrinology, March 1, 2009; 150(3): 1341 - 1352.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
D. L. Kleinberg, T. L. Wood, P. A. Furth, and A. V. Lee
Growth Hormone and Insulin-Like Growth Factor-I in the Transition from Normal Mammary Development to Preneoplastic Mammary Lesions
Endocr. Rev., February 1, 2009; 30(1): 51 - 74.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
V. Pandey, J. K. Perry, K. M. Mohankumar, X.-J. Kong, S.-M. Liu, Z.-S. Wu, M. D. Mitchell, T. Zhu, and P. E. Lobie
Autocrine Human Growth Hormone Stimulates Oncogenicity of Endometrial Carcinoma Cells
Endocrinology, August 1, 2008; 149(8): 3909 - 3919.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. M. Mohankumar, J. K. Perry, N. Kannan, K. Kohno, P. D. Gluckman, B. S. Emerald, and P. E. Lobie
Transcriptional Activation of Signal Transducer and Activator of Transcription (STAT) 3 and STAT5B Partially Mediate Homeobox A1-Stimulated Oncogenic Transformation of the Immortalized Human Mammary Epithelial Cell
Endocrinology, May 1, 2008; 149(5): 2219 - 2229.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. J. van den Eijnden and G. J. Strous
Autocrine Growth Hormone: Effects on Growth Hormone Receptor Trafficking and Signaling
Mol. Endocrinol., November 1, 2007; 21(11): 2832 - 2846.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Q. Shen, D. D. Lantvit, Q. Lin, Y. Li, K. Christov, Z. Wang, T. G. Unterman, R. G. Mehta, and S. M. Swanson
Advanced Rat Mammary Cancers Are Growth Hormone Dependent
Endocrinology, October 1, 2007; 148(10): 4536 - 4544.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. Seoane, I. Ben, V. Centeno, and R. Perez-Fernandez
Cellular Expression Levels of the Vitamin D Receptor Are Critical to Its Transcriptional Regulation by the Pituitary Transcription Factor Pit-1
Mol. Endocrinol., July 1, 2007; 21(7): 1513 - 1525.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
H.-J. Kim, B. C. Litzenburger, X. Cui, D. A. Delgado, B. C. Grabiner, X. Lin, M. T. Lewis, M. M. Gottardis, T. W. Wong, R. M. Attar, et al.
Constitutively Active Type I Insulin-Like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and Is Accompanied by an Epithelial-to-Mesenchymal Transition Mediated by NF-{kappa}B and Snail
Mol. Cell. Biol., April 15, 2007; 27(8): 3165 - 3175.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Polgar, B. Fogelgren, J. M. Shipley, and K. Csiszar
Lysyl Oxidase Interacts with Hormone Placental Lactogen and Synergistically Promotes Breast Epithelial Cell Proliferation and Migration
J. Biol. Chem., February 2, 2007; 282(5): 3262 - 3272.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. S. Emerald, Y. Chen, T. Zhu, Z. Zhu, K.-O. Lee, P. D. Gluckman, and P. E. Lobie
{alpha}CP1 Mediates Stabilization of hTERT mRNA by Autocrine Human Growth Hormone
J. Biol. Chem., January 5, 2007; 282(1): 680 - 690.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Mukhina, D. Liu, K. Guo, M. Raccurt, S. Borges-Bendris, H. C. Mertani, and P. E. Lobie
Autocrine Growth Hormone Prevents Lactogenic Differentiation of Mouse Mammary Epithelial Cells
Endocrinology, April 1, 2006; 147(4): 1819 - 1829.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Zhang, B. S. Emerald, S. Mukhina, K. M. Mohankumar, A. Kraemer, A. S. Yap, P. D. Gluckman, K.-O. Lee, and P. E. Lobie
HOXA1 Is Required for E-cadherin-dependent Anchorage-independent Survival of Human Mammary Carcinoma Cells
J. Biol. Chem., March 10, 2006; 281(10): 6471 - 6481.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Q. Xu, B. S. Emerald, E. L. K. Goh, N. Kannan, L. D. Miller, P. D. Gluckman, E. T. Liu, and P. E. Lobie
Gene Expression Profiling to Identify Oncogenic Determinants of Autocrine Human Growth Hormone in Human Mammary Carcinoma
J. Biol. Chem., June 24, 2005; 280(25): 23987 - 24003.
[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 © 2005 by the American Association for Cancer Research.