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 Lee, E. J.
Right arrow Articles by Jameson, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, E. J.
Right arrow Articles by Jameson, J. L.
The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 2 786-794
Copyright © 1999 by The Endocrine Society

Original Studies

Targeted Expression of Toxic Genes Directed by Pituitary Hormone Promoters: A Potential Strategy for Adenovirus-Mediated Gene Therapy of Pituitary Tumors1

Eun Jig Lee, Leonard M. Anderson, Bayar Thimmapaya and J. Larry Jameson

Division of Endocrinology, Metabolism, and Molecular Medicine (E.J.L., J.L.J.) and the Department of Microbiology/Immunobiology (L.M.A., B.T.), Northwestern University Medical School, Chicago, Illinois 60611

Address all correspondence and requests for reprints to: J. Larry Jameson, M.D., Ph.D., Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois 60611. E-mail: ljameson{at}nwu.edu

Pituitary adenomas cause clinical manifestations because of mass effects and excess hormone production. This group of tumors represents a tractable target for gene therapy because they are rarely metastatic and because reductions in tumor size and function, in addition to those achieved after surgery, may be of clinical benefit. In this report we describe a strategy for targeting the expression of toxic genes to pituitary cells using adenoviral vectors. Pituitary hormone promoters (human GH or glycoprotein hormone {alpha}-subunit) were used to express either a marker gene [ß-galactosidase (ß-gal)] or a toxic gene [herpes simplex virus thymidine kinase (TK)]. In GH-producing GH3 cells and in {alpha}-subunit-producing pituitary tumor cell lines, recombinant adenoviruses containing either the {alpha}-subunit promoter (Ad{alpha}Gal; Ad{alpha}TK) or the GH promoter (AdGHGal; AdGHTK) were expressed at high levels. Using histological studies and assays for ß-gal activity, expression was shown to persist for at least 21 days, and it was relatively selective for pituitary cell lines. Cytotoxicity studies were performed using the TK-containing vectors and treatment with ganciclovir. Both AdGHTK and Ad{alpha}TK caused greater than 95% cytotoxicity of GH3 and {alpha}T3 cells, respectively, at a viral dose (multiplicity of infection, 5 plaque-forming units/cell) that induced minimal toxicity using control viruses. Little cellular toxicity was seen using a nonpituitary cell line (T47D breast tumor cells). The AdGHTK virus also caused marked reduction in the size of GH3 cell tumors that were propagated in nude mice. These studies suggest that adenoviral vectors carrying human pituitary gland specific promoters may be useful for developing gene therapy strategies for the treatment of pituitary adenomas.




This article has been cited by other articles:


Home page
 J EndocrinolHome page
Z. Wang, T. Mitsui, M. Ishida, and J. Arita
Adenovirus vectors differentially modulate proliferation of pituitary lactotrophs in primary culture in a mitogen and infection time-dependent manner
J. Endocrinol., July 1, 2008; 198(1): 209 - 217.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
M Candolfi, G Jaita, D Pisera, L Ferrari, C Barcia, C Liu, J Yu, G Liu, M G Castro, and A Seilicovich
Adenoviral vectors encoding tumor necrosis factor-{alpha} and FasL induce apoptosis of normal and tumoral anterior pituitary cells.
J. Endocrinol., June 1, 2006; 189(3): 681 - 690.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. E. Burdette, J. S. Jeruss, S. J. Kurley, E. J. Lee, and T. K. Woodruff
Activin A Mediates Growth Inhibition and Cell Cycle Arrest through Smads in Human Breast Cancer Cells
Cancer Res., September 1, 2005; 65(17): 7968 - 7975.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
E. J. Lee and J L. Jameson
Gene therapy of pituitary diseases
J. Endocrinol., June 1, 2005; 185(3): 353 - 362.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
E. J. Lee, T. Russell, L. Hurley, and J. L. Jameson
Pituitary Transcription Factor-1 Induces Transient Differentiation of Adult Hepatic Stem Cells into Prolactin-Producing Cells in Vivo
Mol. Endocrinol., April 1, 2005; 19(4): 964 - 971.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Park, E. T. Maizels, Z. J. Feiger, H. Alam, C. A. Peters, T. K. Woodruff, T. G. Unterman, E. J. Lee, J. L. Jameson, and M. Hunzicker-Dunn
Induction of Cyclin D2 in Rat Granulosa Cells Requires FSH-dependent Relief from FOXO1 Repression Coupled with Positive Signals from Smad
J. Biol. Chem., March 11, 2005; 280(10): 9135 - 9148.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
C. Roche, A. J Zamora, D. Taieb, E. Lavaque, R. Rasolonjanahary, H. Dufour, C. Bagnis, A. Enjalbert, and A. Barlier
Lentiviral vectors efficiently transduce human gonadotroph and somatotroph adenomas in vitro. Targeted expression of transgene by pituitary hormone promoters
J. Endocrinol., October 1, 2004; 183(1): 217 - 233.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. P. Gillam, A. R. Sidhaye, E. J. Lee, J. Rutishauser, C. W. Stephan, and P. Kopp
Functional Characterization of Pendrin in a Polarized Cell System: EVIDENCE FOR PENDRIN-MEDIATED APICAL IODIDE EFFLUX
J. Biol. Chem., March 26, 2004; 279(13): 13004 - 13010.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
L. Barzon, M. Boscaro, and G. Palu
Endocrine Aspects of Cancer Gene Therapy
Endocr. Rev., February 1, 2004; 25(1): 1 - 44.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
W. Liu, C. Chin-Chance, E.-J. Lee, and W. L. Lowe Jr.
Activation of Phosphatidylinositol 3-Kinase Contributes to Insulin-Like Growth Factor I-Mediated Inhibition of Pancreatic {beta}-Cell Death
Endocrinology, October 1, 2002; 143(10): 3802 - 3812.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. S. Sarac, S. Windeatt, M. G. Castro, and I. Lindberg
Intrapituitary Adenoviral Administration of 7B2 Can Extend Life Span and Reverse Endocrinological Deficiencies in 7B2 Null Mice
Endocrinology, June 1, 2002; 143(6): 2314 - 2323.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. Zhang, F. H. Straus, and L. J. DeGroot
Cell-Specific Viral Gene Therapy of a Hurthle Cell Tumor
J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1407 - 1414.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. J. Lee, W. R. Duan, M. Jakacka, B. D. Gehm, and J. L. Jameson
Dominant Negative ER Induces Apoptosis in GH4 Pituitary Lactotrope Cells and Inhibits Tumor Growth in Nude Mice
Endocrinology, September 1, 2001; 142(9): 3756 - 3763.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
E. J. Lee, F. Martinson, T. Kotlar, B. Thimmapaya, and J. L. Jameson
Adenovirus-Mediated Targeted Expression of Toxic Genes to Adrenocorticotropin-Producing Pituitary Tumors Using the Proopiomelanocortin Promoter
J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3400 - 3409.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. R. Smith-Arica, J. C. Williams, D. Stone, J. Smith, P. R. Lowenstein, and M. G. Castro
Switching On and Off Transgene Expression within Lactotrophic Cells in the Anterior Pituitary Gland in Vivo
Endocrinology, June 1, 2001; 142(6): 2521 - 2532.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
U. B. Kaiser
Editorial: Pituitary Gene Therapy--Hypotheses on the Hypophysis
Endocrinology, February 1, 2001; 142(2): 528 - 531.
[Full Text] [PDF]

Home page
 EndocrinologyHome page
J. R. E. Davis, J. McVerry, G. A. Lincoln, S. Windeatt, P. R. Lowenstein, M. G. Castro, and A. S. McNeilly
Cell Type-Specific Adenoviral Transgene Expression in the Intact Ovine Pituitary Gland after Stereotaxic Delivery: An in VivoSystem for Long-Term Multiple Parameter Evaluation of Human Pituitary Gene Therapy
Endocrinology, February 1, 2001; 142(2): 795 - 801.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. J. Lee, W. R. Duan, T. Kotlar, and J. L. Jameson
Restoration of Growth Hormone-Releasing Hormone (GHRH) Responsiveness in Pituitary GH3 Cells by Adenovirus-Directed Expression of the Human GHRH Receptor
Endocrinology, January 1, 2001; 142(1): 414 - 420.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. D. Southgate, D. Stone, J. C. Williams, P. R. Lowenstein, and M. G. Castro
Long-Term Transgene Expression within the Anterior Pituitary Gland in Situ: Impact on Circulating Hormone Levels, Cellular and Antibody-Mediated Immune Responses
Endocrinology, January 1, 2001; 142(1): 464 - 476.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. D. Southgate, S. Windeatt, J. Smith-Arica, C. A. Gerdes, M. J. Perone, I. Morris, J. R. E. Davis, D. Klatzmann, P. R. Lowenstein, and M. G. Castro
Transcriptional Targeting to Anterior Pituitary Lactotrophic Cells Using Recombinant Adenovirus Vectors in Vitro and in Vivo in Normal and Estrogen/Sulpiride-Induced Hyperplasic Anterior Pituitaries
Endocrinology, September 1, 2000; 141(9): 3493 - 3505.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Windeatt, T. D. Southgate, R. A. Dewey, F. Bolognani, M. J. Perone, A. T. Larregina, T. C. Maleniak, I. D. Morris, R. G. Goya, D. Klatzmann, et al.
Adenovirus-Mediated Herpes Simplex Virus Type-1 Thymidine Kinase Gene Therapy Suppresses Oestrogen-Induced Pituitary Prolactinomas
J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1296 - 1305.
[Abstract] [Full Text]


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 © 1999 by The Endocrine Society