help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ishikawa, H.
Right arrow Articles by Melmed, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ishikawa, H.
Right arrow Articles by Melmed, S.
The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 2 867-874
Copyright © 2001 by The Endocrine Society

Original Studies

Human Pituitary Tumor-Transforming Gene Induces Angiogenesis1

Hiroki Ishikawa, Anthony P. Heaney, Run Yu, Gregory A. Horwitz and Shlomo Melmed

Cedars-Sinai Research Institute, University of California School of Medicine, Los Angeles, California 90048

Address all correspondence and requests for reprints to: Shlomo Melmed, M.D., Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 2015, Los Angeles, California 90048. E-mail: melmed{at}csmc.edu

Angiogenesis is a key determinant and rate-limiting step in tumor progression and metastatic spread. As pituitary tumor-transforming gene (PTTG) induces basic fibroblast growth factor (bFGF), we tested angiogenesis induced by conditioned medium (CM) derived from NIH-3T3 transfectants overexpressing wild-type human PTTG (WT-hPTTG-CM). We also examined the relationship between PTTG expression and tumor vascularity in a series of human tumors. CM from Wt-hPTTG transfectants induced proliferation, migration, and tube formation of human umbilical vein endothelial cells in vitro. The bFGF concentration in WT-hPTTG-CM was elevated (10.5 ± 0.56) compared with CM from nontransfected NIH-3T3 cells (3.3 ± 0.56 pg/mL), and addition of anti-bFGF antibody to CM abrogated these angiogenesis markers (P < 0.01). In vivo, concentrated WT-hPTTG-CM induced chick chorioallantoic membrane spoke-wheel-like appearances. Moreover, CM derived from hPTTG transfectants harboring a point mutation on the C-terminus proline-rich region of PTTG induced weaker angiogenic activity than WT-hPTTG-CM (P < 0.01). Thus, human PTTG induces an angiogenic phenotype in both in vitro and in vivo angiogenesis models, and high PTTG messenger ribonucleic acid is associated with an angiogenic phenotype in human tumors. These PTTG-directed angiogenic actions may be mediated through bFGF, which also contributes to tumor growth.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
S. Yan, C. Zhou, X. Lou, Z. Xiao, H. Zhu, Q. Wang, Y. Wang, N. Lu, S. He, Q. Zhan, et al.
PTTG Overexpression Promotes Lymph Node Metastasis in Human Esophageal Squamous Cell Carcinoma
Cancer Res., April 15, 2009; 69(8): 3283 - 3290.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
F. Salehi, K. Kovacs, B. W Scheithauer, R. V Lloyd, and M. Cusimano
Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update
Endocr. Relat. Cancer, September 1, 2008; 15(3): 721 - 743.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. C. Limon-Mortes, M. Mora-Santos, A. Espina, J. A. Pintor-Toro, A. Lopez-Roman, M. Tortolero, and F. Romero
UV-induced degradation of securin is mediated by SKP1-CUL1-{beta}TrCP E3 ubiquitin ligase
J. Cell Sci., June 1, 2008; 121(11): 1825 - 1831.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
V. Chesnokova, S. Zonis, T. Rubinek, R. Yu, A. Ben-Shlomo, K. Kovacs, K. Wawrowsky, and S. Melmed
Senescence Mediates Pituitary Hypoplasia and Restrains Pituitary Tumor Growth
Cancer Res., November 1, 2007; 67(21): 10564 - 10572.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. Cristina, G. Diaz-Torga, A. Gongora, M. C. Guida, M. I. Perez-Millan, A. Baldi, and D. Becu-Villalobos
Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice
Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1341 - E1351.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
S. M El-Naggar, M. T Malik, A. Martin, J. P Moore, M. Proctor, T. Hamid, and S. S Kakar
Development of cystic glandular hyperplasia of the endometrium in Mullerian inhibitory substance type II receptor-pituitary tumor transforming gene transgenic mice
J. Endocrinol., July 1, 2007; 194(1): 179 - 191.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
C. S. Kim, H. Ying, M. C. Willingham, and S.-y. Cheng
The pituitary tumor-transforming gene promotes angiogenesis in a mouse model of follicular thyroid cancer
Carcinogenesis, May 1, 2007; 28(5): 932 - 939.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
G. Vlotides, T. Eigler, and S. Melmed
Pituitary Tumor-Transforming Gene: Physiology and Implications for Tumorigenesis
Endocr. Rev., April 1, 2007; 28(2): 165 - 186.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
G. Vlotides, M. Cruz-Soto, T. Rubinek, T. Eigler, C. J. Auernhammer, and S. Melmed
Mechanisms for Growth Factor-Induced Pituitary Tumor Transforming Gene-1 Expression in Pituitary Folliculostellate TtT/GF Cells
Mol. Endocrinol., December 1, 2006; 20(12): 3321 - 3335.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. S. Kim, J. A. Franklyn, K. Boelaert, M. C. Eggo, J. C. Watkinson, and C. J. McCabe
Pituitary Tumor Transforming Gene (PTTG) Stimulates Thyroid Cell Proliferation via a Vascular Endothelial Growth Factor/Kinase Insert Domain Receptor/Inhibitor of DNA Binding-3 Autocrine Pathway
J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4603 - 4611.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
R. Yu, M. Cruz-Soto, S. L. Calzi, H. Hui, and S. Melmed
Murine pituitary tumor-transforming gene functions as a securin protein in insulin-secreting cells.
J. Endocrinol., October 1, 2006; 191(1): 45 - 53.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
I. Donangelo, S. Gutman, E. Horvath, K. Kovacs, K. Wawrowsky, M. Mount, and S. Melmed
Pituitary Tumor Transforming Gene Overexpression Facilitates Pituitary Tumor Development
Endocrinology, October 1, 2006; 147(10): 4781 - 4791.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
N. Chattopadhyay
Effects of calcium-sensing receptor on the secretion of parathyroid hormone-related peptide and its impact on humoral hypercalcemia of malignancy
Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E761 - E770.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. S. Kim, J. A. Franklyn, A. L. Stratford, K. Boelaert, J. C. Watkinson, M. C. Eggo, and C. J. McCabe
Pituitary Tumor-Transforming Gene Regulates Multiple Downstream Angiogenic Genes in Thyroid Cancer
J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1119 - 1128.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
V. Chesnokova, K. Kovacs, A.-V. Castro, S. Zonis, and S. Melmed
Pituitary Hypoplasia in Pttg-/- Mice Is Protective for Rb+/- Pituitary Tumorigenesis
Mol. Endocrinol., September 1, 2005; 19(9): 2371 - 2379.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. L. Stratford, K. Boelaert, L. A. Tannahill, D. S. Kim, A. Warfield, M. C. Eggo, N. J. L. Gittoes, L. S. Young, J. A. Franklyn, and C. J. McCabe
Pituitary Tumor Transforming Gene Binding Factor: A Novel Transforming Gene in Thyroid Tumorigenesis
J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4341 - 4349.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
K Boelaert, R Yu, L A Tannahill, A L Stratford, F L Khanim, M C Eggo, J S Moore, L S Young, N J L Gittoes, J A Franklyn, et al.
PTTG's C-terminal PXXP motifs modulate critical cellular processes in vitro
J. Mol. Endocrinol., December 1, 2004; 33(3): 663 - 677.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. Tfelt-Hansen, S. Yano, S. Bandyopadhyay, R. Carroll, E. M. Brown, and N. Chattopadhyay
Expression of Pituitary Tumor Transforming Gene (PTTG) and Its Binding Protein in Human Astrocytes and Astrocytoma Cells: Function and Regulation of PTTG in U87 Astrocytoma Cells
Endocrinology, September 1, 2004; 145(9): 4222 - 4231.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Kazemi, S. Papadopoulou, S. Li, Q. Su, S. Wang, A. Yoshimura, G. Matlashewski, T. E. Dever, and A. E. Koromilas
Control of {alpha} Subunit of Eukaryotic Translation Initiation Factor 2 (eIF2{alpha}) Phosphorylation by the Human Papillomavirus Type 18 E6 Oncoprotein: Implications for eIF2{alpha}-Dependent Gene Expression and Cell Death
Mol. Cell. Biol., April 15, 2004; 24(8): 3415 - 3429.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. Tfelt-Hansen, P. Schwarz, E. F. Terwilliger, E. M. Brown, and N. Chattopadhyay
Calcium-Sensing Receptor Induces Messenger Ribonucleic Acid of Human Securin, Pituitary Tumor Transforming Gene, in Rat Testicular Cancer
Endocrinology, December 1, 2003; 144(12): 5188 - 5193.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
H. E. Turner, A. L. Harris, S. Melmed, and J. A. H. Wass
Angiogenesis in Endocrine Tumors
Endocr. Rev., October 1, 2003; 24(5): 600 - 632.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
K. BOELAERT, L. A. TANNAHILL, J. N. BULMER, S. KACHILELE, S. Y. CHAN, D. KIM, N. J. L. GITTOES, J. A. FRANKLYN, M. D. KILBY, and C. J. MCCABE
A potential role for PTTG/securin in the developing human fetal brain
FASEB J, September 1, 2003; 17(12): 1631 - 1639.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
G. A. Horwitz, I. Miklovsky, A. P. Heaney, S.-G. Ren, and S. Melmed
Human Pituitary Tumor-Transforming Gene (PTTG1) Motif Suppresses Prolactin Expression
Mol. Endocrinol., April 1, 2003; 17(4): 600 - 609.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Zhou, K. R. Mehta, A. P. Choi, S. Scolavino, and X. Zhang
DNA Damage-induced Inhibition of Securin Expression Is Mediated by p53
J. Biol. Chem., January 3, 2003; 278(1): 462 - 470.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. J. McCabe, K. Boelaert, L. A. Tannahill, A. P. Heaney, A. L. Stratford, J. S. Khaira, S. Hussain, M. C. Sheppard, J. A. Franklyn, and N. J. L. Gittoes
Vascular Endothelial Growth Factor, Its Receptor KDR/Flk-1, and Pituitary Tumor Transforming Gene in Pituitary Tumors
J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4238 - 4244.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. P. Heaney, V. Nelson, M. Fernando, and G. Horwitz
Transforming Events in Thyroid Tumorigenesis and Their Association with Follicular Lesions
J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 5025 - 5032.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society