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
[Cancer Research 47, 4020-4024, August 1, 1987]
© 1987 American Association for Cancer Research
This Article
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 Gottardis, M. M.
Right arrow Articles by Jordan, V. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gottardis, M. M.
Right arrow Articles by Jordan, V. C.

Antitumor Actions of Keoxifene and Tamoxifen in the N-Nitrosomethylurea-induced Rat Mammary Carcinoma Model1

Marco M. Gottardis and V. Craig Jordan2

Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison, Wisconsin 53792

We have compared the antitumor activities of the antiestrogens, keoxifene (LY 156758) and tamoxifen (TAM), using the N-nitrosomethylurea (NMU) rat mammary carcinoma model.

To establish an effective antitumor dose of TAM in this model, rats were treated 2 wk after initiation with NMU for 8 wk with s.c. daily injections of 6.25 µg, 25 µg, or 100 µg of TAM in peanut oil. At the 25-µg and 100-µg daily doses, TAM completely inhibited tumor appearance during the therapy period. An effective antitumor dose of TAM (100 µg daily) was compared to 20-, 100-, or 500-µg daily doses of keoxifene 7 wk after NMU initiation. None of the keoxifene-treated groups prevented the appearance of tumors as effectively as TAM during 13 wk of therapy. When keoxifene was compared to TAM at equivalent daily doses of 100 and 500 µg daily starting 2 wk after NMU injection, the keoxifene groups again failed to prevent the appearance of all tumors during 10 wk of therapy. TAM, however, completely suppressed any tumor formation.

In the same experiment, animals treated with 500 µg of TAM had therapy stopped after 10 wk, and tumors started to appear 6 wk later. No tumors appeared when animals (n = 25) were treated continuously for 23 wk with 100 µg of TAM.

In separate experiments, keoxifene (500 µg daily) and TAM (500 µg and 100 µg daily) administered for 1 wk blocked the binding of [3H]-estradiol in NMU tumors and in uteri. The effect lasted for up to 5 wk after antiestrogen therapy was stopped.

These experiments demonstrate that keoxifene is not as effective in its antitumor action as TAM in the NMU model.

1 This investigation was supported by USPHS Grant P01 CA-20432, awarded by the National Cancer Institute.

2 To whom requests for reprints should be addressed, at Department of Human Oncology, University of Wisconsin Clinical Cancer Center, 600 Highland Ave., Madison, WI 53792.

Received 1/20/87. Revised 5/ 6/87. Accepted 5/ 8/87.




This article has been cited by other articles:


Home page
 JCOHome page
V. C. Jordan
The 38th David A. Karnofsky Lecture: The Paradoxical Actions of Estrogen in Breast Cancer--Survival or Death?
J. Clin. Oncol., June 20, 2008; 26(18): 3073 - 3082.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
V. C. Jordan
The Rise of Raloxifene and the Fall of Invasive Breast Cancer
J Natl Cancer Inst, June 18, 2008; 100(12): 831 - 833.
[Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
R. A. Lubet, E. Szabo, K. Christov, A. M. Bode, M. E. Ericson, V. E. Steele, M. M. Juliana, and C. J. Grubbs
Effects of gefitinib (Iressa) on mammary cancers: preventive studies with varied dosages, combinations with vorozole or targretin, and biomarker changes
Mol. Cancer Ther., April 1, 2008; 7(4): 972 - 979.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
V. C. Jordan and B. W. O'Malley
Selective Estrogen-Receptor Modulators and Antihormonal Resistance in Breast Cancer
J. Clin. Oncol., December 20, 2007; 25(36): 5815 - 5824.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
V. C. Jordan
Tamoxifen or Raloxifene for Breast Cancer Chemoprevention: A Tale of Two Choices Point
Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2207 - 2209.
[Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
V. C. Jordan
SERMs: Meeting the Promise of Multifunctional Medicines
J Natl Cancer Inst, March 7, 2007; 99(5): 350 - 356.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
R. T Chatterton Jr, J. Zujewski, E. T Mateo, J. Eng-Wong, and V C. Jordan
Effect of raloxifene on salivary sex steroid concentrations in premenopausal women
J. Endocrinol., December 1, 2006; 191(3): 599 - 604.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
B. Malewicz, Z. Wang, C. Jiang, J. Guo, M. P. Cleary, J. P. Grande, and J. Lu
Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary supplements
Carcinogenesis, September 1, 2006; 27(9): 1739 - 1747.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
V. C. Jordan
The Science of Selective Estrogen Receptor Modulators: Concept to Clinical Practice
Clin. Cancer Res., September 1, 2006; 12(17): 5010 - 5013.
[Full Text] [PDF]

Home page
 CarcinogenesisHome page
R. Yao, Y. Wang, Y. Lu, W. J. Lemon, D. W. End, C. J. Grubbs, R. A. Lubet, and M. You
Efficacy of the farnesyltransferase inhibitor R115777 in a rat mammary tumor model: role of Ha-ras mutations and use of microarray analysis in identifying potential targets
Carcinogenesis, July 1, 2006; 27(7): 1420 - 1431.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
V. G. Vogel, J. P. Costantino, D. L. Wickerham, W. M. Cronin, R. S. Cecchini, J. N. Atkins, T. B. Bevers, L. Fehrenbacher, E. R. Pajon Jr, J. L. Wade III, et al.
Effects of Tamoxifen vs Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes: The NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial
JAMA, June 21, 2006; 295(23): 2727 - 2741.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
H. Gogas, C. Markopoulos, and R. Blamey
Should women be advised to take prophylactic endocrine treatment outside of a clinical trial setting?
Ann. Onc., December 1, 2005; 16(12): 1861 - 1866.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
K-M Rau, H-Y Kang, T-L Cha, S A Miller, and M-C Hung
The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers
Endocr. Relat. Cancer, September 1, 2005; 12(3): 511 - 532.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. I. Vanzulli, R. Soldati, R. Meiss, L. Colombo, A. A. Molinolo, and C. Lanari
Estrogen or antiprogestin treatment induces complete regression of pulmonary and axillary metastases in an experimental model of breast cancer progression
Carcinogenesis, June 1, 2005; 26(6): 1055 - 1063.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
C. L. Smith and B. W. O'Malley
Coregulator Function: A Key to Understanding Tissue Specificity of Selective Receptor Modulators
Endocr. Rev., February 1, 2004; 25(1): 45 - 71.
[Abstract] [Full Text] [PDF]

Home page
 Jpn J Clin OncolHome page
T. Kakizoe
Chemoprevention of Cancer - Focusing on Clinical Trials
Jpn. J. Clin. Oncol., September 1, 2003; 33(9): 421 - 442.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. V. Jensen and V. C. Jordan
The Estrogen Receptor: A Model for Molecular Medicine
Clin. Cancer Res., June 1, 2003; 9(6): 1980 - 1989.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
F. J. Esteva, J. Glaspy, S. Baidas, L. Laufman, L. Hutchins, M. Dickler, D. Tripathy, R. Cohen, A. DeMichele, R. C. Yocum, et al.
Multicenter Phase II Study of Oral Bexarotene for Patients With Metastatic Breast Cancer
J. Clin. Oncol., March 15, 2003; 21(6): 999 - 1006.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
K. J. Ho and J. K. Liao
Nonnuclear Actions of Estrogen
Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 1952 - 1961.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
E. Galbiati, P. L. Caruso, G. Amari, E. Armani, S. Ghirardi, M. Delcanale, and M. Civelli
Pharmacological Actions of a Novel, Potent, Tissue-Selective Benzopyran Estrogen
J. Pharmacol. Exp. Ther., October 1, 2002; 303(1): 196 - 203.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. Cucinelli, L. Soranna, D. Romualdi, G. Muzj, S. Mancuso, and A. Lanzone
The Effect of Raloxifene on Glyco-Insulinemic Homeostasis in Healthy Postmenopausal Women: A Randomized Placebo-Controlled Study
J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4186 - 4192.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. S. Levenson, K. M. Svoboda, K. M. Pease, S. A. Kaiser, B. Chen, L. A. Simons, B. D. Jovanovic, P. A. Dyck, and V. C. Jordan
Gene Expression Profiles with Activation of the Estrogen Receptor {alpha}-Selective Estrogen Receptor Modulator Complex in Breast Cancer Cells Expressing Wild-Type Estrogen Receptor
Cancer Res., August 1, 2002; 62(15): 4419 - 4426.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Liu, W.-C. Park, D. J. Bentrem, K. P. McKian, A. D. L. Reyes, J. A. Loweth, J. M. Schafer, J. W. Zapf, and V. C. Jordan
Structure-Function Relationships of the Raloxifene-Estrogen Receptor-alpha Complex for Regulating Transforming Growth Factor-alpha Expression in Breast Cancer Cells
J. Biol. Chem., March 8, 2002; 277(11): 9189 - 9198.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Suh, A. L. Glasebrook, A. D. Palkowitz, H. U. Bryant, L. L. Burris, J. J. Starling, H. L. Pearce, C. Williams, C. Peer, Y. Wang, et al.
Arzoxifene, a New Selective Estrogen Receptor Modulator for Chemoprevention of Experimental Breast Cancer
Cancer Res., December 1, 2001; 61(23): 8412 - 8415.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. A. Cohen, B. Pittman, C.-X. Wang, C. Aliaga, L. Yu, and J. D. Moyer
LAS, a Novel Selective Estrogen Receptor Modulator with Chemopreventive and Therapeutic Activity in the N-Nitroso-N-methylurea-induced Rat Mammary Tumor Model
Cancer Res., December 1, 2001; 61(24): 8683 - 8688.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
V. C. Jordan, S. Gapstur, and M. Morrow
Selective Estrogen Receptor Modulation and Reduction in Risk of Breast Cancer, Osteoporosis, and Coronary Heart Disease
J Natl Cancer Inst, October 3, 2001; 93(19): 1449 - 1457.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
J. R. Benson
Re: Five Versus More Than Five Years of Tamoxifen for Lymph Node-Negative Breast Cancer: Updated Findings From the National Surgical Adjuvant Breast and Bowel Project B-14 Randomized Trial
J Natl Cancer Inst, October 3, 2001; 93(19): 1493 - 1494.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
J. E. Green, M.-A. Shibata, E. Shibata, R. C. Moon, M. R. Anver, G. Kelloff, and R. Lubet
2-Difluoromethylornithine and Dehydroepiandrosterone Inhibit Mammary Tumor Progression but not Mammary or Prostate Tumor Initiation in C3(1)/SV40 T/t-antigen Transgenic Mice
Cancer Res., October 1, 2001; 61(20): 7449 - 7455.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
V. C. Jordan
Selective Estrogen Receptor Modulation: A Personal Perspective
Cancer Res., August 1, 2001; 61(15): 5683 - 5687.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. M. Schafer, E.-S. Lee, R. C. Dardes, D. Bentrem, R. M. O'Regan, A. De Los Reyes, and V. C. Jordan
Analysis of Cross-Resistance of the Selective Estrogen Receptor Modulators Arzoxifene (LY353381) and LY117018 in Tamoxifen-stimulated Breast Cancer Xenografts
Clin. Cancer Res., August 1, 2001; 7(8): 2505 - 2512.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
V. C. Jordan
Estrogen, Selective Estrogen Receptor Modulation, and Coronary Heart Disease: Something or Nothing
J Natl Cancer Inst, January 3, 2001; 93(1): 2 - 4.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
V. R. Agarwal, E. D. Bischoff, T. Hermann, and W. W. Lamph
Induction of Adipocyte-specific Gene Expression Is Correlated with Mammary Tumor Regression by the Retinoid X Receptor-Ligand LGD1069 (Targretin)
Cancer Res., November 1, 2000; 60(21): 6033 - 6038.
[Abstract] [Full Text]

Home page
 JCOHome page
C. K. Osborne and S. A. W. Fuqua
Selective Estrogen Receptor Modulators: Structure, Function, and Clinical Use
J. Clin. Oncol., September 17, 2000; 18(17): 3172 - 3186.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Wu, H.-T. Kim, J. L. Rodriquez, D. Munoz-Medellin, S. K. Mohsin, S. G. Hilsenbeck, W. W. Lamph, M. M. Gottardis, M. A. Shirley, J. G. Kuhn, et al.
9-cis-Retinoic Acid Suppresses Mammary Tumorigenesis in C3(1)-Simian Virus 40 T Antigen-transgenic Mice
Clin. Cancer Res., September 1, 2000; 6(9): 3696 - 3704.
[Abstract] [Full Text]

Home page
 CarcinogenesisHome page
M. B. Sporn and N. Suh
Chemoprevention of cancer
Carcinogenesis, March 1, 2000; 21(3): 525 - 530.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. Hilakivi-Clarke, E. Cho, I. Onojafe, D. J. Liao, and R. Clarke
Maternal Exposure to Tamoxifen during Pregnancy Increases Carcinogen-induced Mammary Tumorigenesis among Female Rat Offspring
Clin. Cancer Res., January 1, 2000; 6(1): 305 - 308.
[Abstract] [Full Text]

Home page
 JNCI J Natl Cancer InstHome page
E. D. Bischoff, R. A. Heyman, and W. W. Lamph
Effect of the Retinoid X Receptor-Selective Ligand LGD1069 on Mammary Carcinoma After Tamoxifen Failure
J Natl Cancer Inst, December 15, 1999; 91(24): 2118 - 2118.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
S. M. Lippman and P. H. Brown
Tamoxifen Prevention of Breast Cancer: an Instance of the Fingerpost
J Natl Cancer Inst, November 3, 1999; 91(21): 1809 - 1819.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
N. Suh, Y. Wang, C. R. Williams, R. Risingsong, T. Gilmer, T. M. Willson, and M. B. Sporn
A New Ligand for the Peroxisome Proliferator-Activated Receptor-{{gamma}} (PPAR-{{gamma}}), GW7845, Inhibits Rat Mammary Carcinogenesis
Cancer Res., November 1, 1999; 59(22): 5671 - 5673.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
V. C. Jordan
Tamoxifen: Too Much of a Good Thing?
J. Clin. Oncol., September 1, 1999; 17(9): 2629 - 2629.
[Full Text] [PDF]

Home page
 BMJHome page
V C. Jordan and M Morrow
Raloxifene as a multifunctional medicine?
BMJ, August 7, 1999; 319(7206): 331 - 332.
[Full Text]

Home page
 JAMAHome page
S. R. Cummings, S. Eckert, K. A. Krueger, D. Grady, T. J. Powles, J. A. Cauley, L. Norton, T. Nickelsen, N. H. Bjarnason, M. Morrow, et al.
The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women: Results From the MORE Randomized Trial
JAMA, June 16, 1999; 281(23): 2189 - 2197.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
V. C. Jordan and M. Morrow
Tamoxifen, Raloxifene, and the Prevention of Breast Cancer
Endocr. Rev., June 1, 1999; 20(3): 253 - 278.
[Abstract] [Full Text]

Home page
 ANN INTERN MEDHome page
W. Khovidhunkit and D. M. Shoback
Clinical Effects of Raloxifene Hydrochloride in Women
Ann Intern Med, March 2, 1999; 130(5): 431 - 439.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
J. I. Macgregor and V. C. Jordan
Basic Guide to the Mechanisms of Antiestrogen Action
Pharmacol. Rev., June 1, 1998; 50(2): 151 - 196.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
K. Yao and V. C. Jordan
Questions about Tamoxifen and the Future Use of Antiestrogens
Oncologist, April 1, 1998; 3(2): 104 - 110.
[Abstract] [Full Text]

Home page
 ScienceHome page
W. K. Hong and M. B. Sporn
Recent Advances in Chemoprevention of Cancer
Science, November 7, 1997; 278(5340): 1073 - 1077.
[Abstract] [Full Text]

Home page
 CirculationHome page
N. H. Bjarnason, J. Haarbo, I. Byrjalsen, R. F. Kauffman, and C. Christiansen
Raloxifene Inhibits Aortic Accumulation of Cholesterol in Ovariectomized, Cholesterol-Fed Rabbits
Circulation, September 16, 1997; 96(6): 1964 - 1969.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
R. F. Kauffman, W. R. Bensch, R. E. Roudebush, H. W. Cole, J. S. Bean, D. L. Phillips, A. Monroe, G. J. Cullinan, A. L. Glasebrook, and H. U. Bryant
Hypocholesterolemic Activity of Raloxifene (LY139481): Pharmacological Characterization as a Selective Estrogen Receptor Modulator
J. Pharmacol. Exp. Ther., January 1, 1997; 280(1): 146 - 153.
[Abstract] [Full Text]


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 © 1987 by the American Association for Cancer Research.