| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Carcinogenesis |
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030
To define the functional relevance of progesterone-initiated intracellular signaling in mammary gland tumorigenesis, the progesterone receptor knockout (PRKO) mouse model was used in the context of an established carcinogen-induced mammary tumorigenesis system. In carcinogen-treated, 7,12-dimethylbenz(a)anthracene (DMBA), pituitary-isografted mice, there was a marked reduction in mammary tumor incidence in PRKO mice as compared with isogenic wild types (WT). Mammary tumors arose in 12 (60%) of 20 WT mice compared with 3 (15%) of 20 PRKO mice by 44 weeks after the initial DMBA treatment. In the absence of a pituitary isograft, mammary tumors developed in 4 (20%) of 20 WT mice versus 4 (20%) of 20 PRKO mice by 47 weeks. At the time of carcinogen administration, the proliferative index of the pituitary-stimulated WT gland was at least 4-fold higher than similarly treated PRKO glands, supporting the importance of PR-mediated proliferative pathways in the genesis of this tumor type. Unlike the WT gland, the PRKO gland was unable to exhibit alveologenesis in response to pituitary isograft stimulation; thus, DMBA-initiated mammary tumors observed in the PRKO were assumed to be exclusively of ductal origin. Compared with previous tested strains, by 47 weeks, a higher incidence of DMBA-induced ovarian tumors was observed in this mouse strain: (a) 4 (20%) of 20 WT mice and 9 (45%) of 20 PRKO mice with a pituitary isograft; and (b) 10 (50%) of 20 WT mice and 10 (50%) of 20 PRKO mice without a pituitary isograft. Despite the host-strain’s underlying propensity for DMBA-induced ovarian neoplasms, our studies underscore the specific importance of the PR (as distinct from the estrogen receptor) as a mandatory mediator for those intracellular signaling pathways that are essential for the initiation of the majority of murine mammary tumors induced by DMBA. Apart from providing strong support for progesterone’s role in mammary gland tumorigenesis as well as furthering our fundamental understanding of breast cancer etiology, these studies may have implications for the routine use of progestins.
This article has been cited by other articles:
|
|
 |
|
  J. P. Lydon and D. P. Edwards Finally! A Model for Progesterone Receptor Action in Normal Human Breast Endocrinology, July 1, 2009; 150(7): 2988 - 2990. [Full Text] [PDF]
|
|
|
|
|
|
J. D. Graham, P. A. Mote, U. Salagame, J. H. van Dijk, R. L. Balleine, L. I. Huschtscha, R. R. Reddel, and C. L. Clarke DNA Replication Licensing and Progenitor Numbers Are Increased by Progesterone in Normal Human Breast Endocrinology, July 1, 2009; 150(7): 3318 - 3326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lanari, C. A Lamb, V. T Fabris, L. A Helguero, R. Soldati, M. C. Bottino, S. Giulianelli, J. P. Cerliani, V. Wargon, and A. Molinolo The MPA mouse breast cancer model: evidence for a role of progesterone receptors in breast cancer Endocr. Relat. Cancer, June 1, 2009; 16(2): 333 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Fernandez-Valdivia, A. Mukherjee, C. J. Creighton, A. C. Buser, F. J. DeMayo, D. P. Edwards, and J. P. Lydon Transcriptional Response of the Murine Mammary Gland to Acute Progesterone Exposure Endocrinology, December 1, 2008; 149(12): 6236 - 6250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Sun, S. Zhang, D. Zhang, Y. Li, X. Zhao, Y. Luo, and Y. Guo Identification of Metastasis-Related Proteins and Their Clinical Relevance to Triple-Negative Human Breast Cancer Clin. Cancer Res., November 1, 2008; 14(21): 7050 - 7059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E Morabito, J. F Trott, D. M Korz, H. E Fairfield, S. H Buck, and R. C Hovey A 5' distal palindrome within the mouse mammary tumor virus-long terminal repeat recruits a mammary gland-specific complex and is required for a synergistic response to progesterone plus prolactin J. Mol. Endocrinol., August 1, 2008; 41(2): 75 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. He, Q. Feng, A. Mukherjee, D. M. Lonard, F. J. DeMayo, B. S. Katzenellenbogen, J. P. Lydon, and B. W. O'Malley A Repressive Role for Prohibitin in Estrogen Signaling Mol. Endocrinol., February 1, 2008; 22(2): 344 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liang, C. Besch-Williford, R. A. Brekken, and S. M. Hyder Progestin-Dependent Progression of Human Breast Tumor Xenografts: A Novel Model for Evaluating Antitumor Therapeutics Cancer Res., October 15, 2007; 67(20): 9929 - 9936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Y. Lee, J.-W. Jeong, J. Wang, L. Ma, J. F. Martin, S. Y. Tsai, J. P. Lydon, and F. J. DeMayo Bmp2 Is Critical for the Murine Uterine Decidual Response Mol. Cell. Biol., August 1, 2007; 27(15): 5468 - 5478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System Endocr. Rev., June 1, 2007; 28(4): 387 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Boonyaratanakornkit, E. McGowan, L. Sherman, M. A. Mancini, B. J. Cheskis, and D. P. Edwards The Role of Extranuclear Signaling Actions of Progesterone Receptor in Mediating Progesterone Regulation of Gene Expression and the Cell Cycle Mol. Endocrinol., February 1, 2007; 21(2): 359 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yang, I. M. Wolf, H. Chen, S. Periyasamy, Z. Chen, W. Yong, S. Shi, W. Zhao, J. Xu, A. Srivastava, et al. FK506-Binding Protein 52 Is Essential to Uterine Reproductive Physiology Controlled by the Progesterone Receptor A Isoform Mol. Endocrinol., November 1, 2006; 20(11): 2682 - 2694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mukherjee, S. M. Soyal, R. Fernandez-Valdivia, M. Gehin, P. Chambon, F. J. DeMayo, J. P. Lydon, and B. W. O'Malley Steroid Receptor Coactivator 2 Is Critical for Progesterone-Dependent Uterine Function and Mammary Morphogenesis in the Mouse Mol. Cell. Biol., September 1, 2006; 26(17): 6571 - 6583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lu, K. Shen, Y. Wang, S. J. Santner, J. Chen, S.C. Brooks, and Y.A. Wang Atm-haploinsufficiency enhances susceptibility to carcinogen-induced mammary tumors Carcinogenesis, April 1, 2006; 27(4): 848 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Q. Kuang, L. Liao, S. Wang, D. Medina, B. W. O'Malley, and J. Xu Mice Lacking the Amplified in Breast Cancer 1/Steroid Receptor Coactivator-3 Are Resistant to Chemical Carcinogen-Induced Mammary Tumorigenesis Cancer Res., September 1, 2005; 65(17): 7993 - 8002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Medina, F. S. Kittrell, J. Hill, A. Shepard, G. Thordarson, and P. Brown Tamoxifen Inhibition of Estrogen Receptor-{alpha}-Negative Mouse Mammary Tumorigenesis Cancer Res., April 15, 2005; 65(8): 3493 - 3496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. U. Agoulnik, X.-W. Tong, D.-C. Fischer, K. Korner, N. E. Atkinson, D. P. Edwards, D. R. Headon, N. L. Weigel, and D. G. Kieback A Germline Variation in the Progesterone Receptor Gene Increases Transcriptional Activity and May Modify Ovarian Cancer Risk J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6340 - 6347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Eason, M. C. Velarde, L. Chatman Jr, S. R. Till, Y. Geng, M. Ferguson, T. M. Badger, and R. C. M. Simmen Dietary Exposure to Whey Proteins Alters Rat Mammary Gland Proliferation, Apoptosis, and Gene Expression during Postnatal Development J. Nutr., December 1, 2004; 134(12): 3370 - 3377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Y. Shi, J. P. Lydon, and M. Zhang Hormonal Defect in Maspin Heterozygous Mice Reveals a Role of Progesterone in Pubertal Ductal Development Mol. Endocrinol., September 1, 2004; 18(9): 2196 - 2207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Gava, C. L. Clarke, K. Byth, R. L. Arnett-Mansfield, and A. deFazio Expression of Progesterone Receptors A and B in the Mouse Ovary during the Estrous Cycle Endocrinology, July 1, 2004; 145(7): 3487 - 3494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yi, A. Shepard, F. Kittrell, B. Mulac-Jericevic, D. Medina, and T. K. Said p19ARF Determines the Balance between Normal Cell Proliferation Rate and Apoptosis during Mammary Gland Development Mol. Biol. Cell, May 1, 2004; 15(5): 2302 - 2311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Hopp, H. L. Weiss, S. G. Hilsenbeck, Y. Cui, D. C. Allred, K. B. Horwitz, and S. A. W. Fuqua Breast Cancer Patients with Progesterone Receptor PR-A-Rich Tumors Have Poorer Disease-Free Survival Rates Clin. Cancer Res., April 15, 2004; 10(8): 2751 - 2760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Q. Kuang, L. Liao, H. Zhang, A. V. Lee, B. W. O'Malley, and J. Xu AIB1/SRC-3 Deficiency Affects Insulin-Like Growth Factor I Signaling Pathway and Suppresses v-Ha-ras-induced Breast Cancer Initiation and Progression in Mice Cancer Res., March 1, 2004; 64(5): 1875 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lu, C. Speers, Y. Zhang, X. Xu, J. Hill, E. Steinbis, J. Celestino, Q. Shen, H. Kim, S. Hilsenbeck, et al. Effect of Epidermal Growth Factor Receptor Inhibitor on Development of Estrogen Receptor-Negative Mammary Tumors J Natl Cancer Inst, December 17, 2003; 95(24): 1825 - 1833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. De Vivo, S. E. Hankinson, G. A. Colditz, and D. J. Hunter A Functional Polymorphism in the Progesterone Receptor Gene Is Associated with an Increase in Breast Cancer Risk Cancer Res., September 1, 2003; 63(17): 5236 - 5238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Mulac-Jericevic, J. P. Lydon, F. J. DeMayo, and O. M. Conneely Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform PNAS, August 19, 2003; 100(17): 9744 - 9749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-L. Zhang, D. Zhang, F. J. Michel, J. L. Blum, F. A. Simmen, and R. C. M. Simmen Selective Interactions of Kruppel-like Factor 9/Basic Transcription Element-binding Protein with Progesterone Receptor Isoforms A and B Determine Transcriptional Activity of Progesterone-responsive Genes in Endometrial Epithelial Cells J. Biol. Chem., June 6, 2003; 278(24): 21474 - 21482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Medina, F. S. Kittrell, A. Shepard, A. Contreras, J. M. Rosen, and J. Lydon Hormone Dependence in Premalignant Mammary Progression Cancer Res., March 1, 2003; 63(5): 1067 - 1072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Rowlands, R. Hakkak, M. J. J. Ronis, and T. M. Badger Altered Mammary Gland Differentiation and Progesterone Receptor Expression in Rats Fed Soy and Whey Proteins Toxicol. Sci., November 1, 2002; 70(1): 40 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Ismail, J. Li, F. J. DeMayo, B. W. O'Malley, and J. P. Lydon A Novel LacZ Reporter Mouse Reveals Complex Regulation of the Progesterone Receptor Promoter During Mammary Gland Development Mol. Endocrinol., November 1, 2002; 16(11): 2475 - 2489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Rulli, A. Kuorelahti, O. Karaer, L. J. Pelliniemi, M. Poutanen, and I. Huhtaniemi Reproductive Disturbances, Pituitary Lactotrope Adenomas, and Mammary Gland Tumors in Transgenic Female Mice Producing High Levels of Human Chorionic Gonadotropin Endocrinology, October 1, 2002; 143(10): 4084 - 4095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Ahola, T. Manninen, N. Alkio, and T. Ylikomi G Protein-Coupled Receptor 30 Is Critical for a Progestin-Induced Growth Inhibition in MCF-7 Breast Cancer Cells Endocrinology, September 1, 2002; 143(9): 3376 - 3384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vanzulli, A. Efeyan, F. Benavides, L. A. Helguero, G. Peters, J. Shen, C. J. Conti, C. Lanari, and A. Molinolo p21, p27 and p53 in estrogen and antiprogestin-induced tumor regression of experimental mouse mammary ductal carcinomas Carcinogenesis, May 1, 2002; 23(5): 749 - 758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. M. Conneely, B. Mulac-Jericevic, F. DeMayo, J. P. Lydon, and B. W. O'Malley Reproductive Functions of Progesterone Receptors Recent Prog. Horm. Res., January 1, 2002; 57(1): 339 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. L. Bhat, D. Lantvit, K. Christov, R. G. Mehta, R. C. Moon, and J. M. Pezzuto Estrogenic and Antiestrogenic Properties of Resveratrol in Mammary Tumor Models Cancer Res., October 1, 2001; 61(20): 7456 - 7463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Mehta, K. P. L. Bhat, M. E. Hawthorne, L. Kopelovich, R. R. Mehta, K. Christov, G. J. Kelloff, V. E. Steele, and J. M. Pezzuto Induction of Atypical Ductal Hyperplasia in Mouse Mammary Gland Organ Culture J Natl Cancer Inst, July 18, 2001; 93(14): 1103 - 1106. [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. GOEPFERT, M. MCCARTHY, F. S. KITTRELL, C. STEPHENS, R. L. ULLRICH, B. R. BRINKLEY, and D. MEDINA Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells FASEB J, November 1, 2000; 14(14): 2221 - 2229. [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 |
