Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 308 (5728): 1589-1592

Copyright © 2005 by the American Association for the Advancement of Science

Uterine Fibroids: The Elephant in the Room

Cheryl Lyn Walker1, and Elizabeth A. Stewart2

Abstract: Uterine fibroids (leiomyomas) have historically been viewed as important chiefly as the major indication for hysterectomy. As new therapies are developed, the heterogeneity of this disease becomes therapeutically relevant. An awareness of the role of genetics, the extracellular matrix, and hormones in tumor etiology is key to understanding this disease.

1 Department of Carcinogenesis, University of Texas and MD Anderson Cancer Center, Park Road 1C, Smithville, TX 78957, USA.
2 Center for Uterine Fibroids, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.

Proceedings from the Third National Institutes of Health International Congress on Advances in Uterine Leiomyoma Research: comprehensive review, conference summary and future recommendations.
J. H. Segars, E. C. Parrott, J. D. Nagel, X. C. Guo, X. Gao, L. S. Birnbaum, V. W. Pinn, and D. Dixon (2014)
Hum. Reprod. Update 20, 309-333
   Abstract »    Full Text »    PDF »
Magnetic Resonance-Guided Focused Ultrasound Myomectomy: Safety, Efficacy, Subsequent Fertility and Quality-of-Life Improvements, A Systematic Review.
S. Gizzo, C. Saccardi, T. S. Patrelli, E. Ancona, M. Noventa, S. Fagherazzi, B. Mozzanega, D. D'Antona, and G. B. Nardelli (2014)
Reproductive Sciences 21, 465-476
   Abstract »    Full Text »    PDF »
The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy.
R. Tal and J. H. Segars (2014)
Hum. Reprod. Update 20, 194-216
   Abstract »    Full Text »    PDF »
Antitumor Effects of Flavopiridol on Human Uterine Leiomyoma In Vitro and in a Xenograft model.
H.-G. Lee, J.-W. Baek, S.-J. Shin, S.-H. Kwon, S.-D. Cha, W.-J. Park, R. Chung, E.-S. Choi, G.-H. Lee, and C.-H. Cho (2014)
Reproductive Sciences
   Abstract »    Full Text »    PDF »
Comparative expression of thioredoxin-1 in uterine leiomyomas and myometrium.
P. Hou, L. Zhao, Y. Li, F. Luo, S. Wang, J. Song, and J. Bai (2014)
Mol. Hum. Reprod. 20, 148-154
   Abstract »    Full Text »    PDF »
1,25-Dihydroxyvitamin D3 Reduces Extracellular Matrix-Associated Protein Expression in Human Uterine Fibroid Cells.
S. K. Halder, K. G. Osteen, and A. Al-Hendy (2013)
Biol Reprod 89, 150
   Abstract »    Full Text »    PDF »
Paracrine activation of WNT/{beta}-catenin pathway in uterine leiomyoma stem cells promotes tumor growth.
M. Ono, P. Yin, A. Navarro, M. B. Moravek, J. S. Coon V, S. A. Druschitz, V. A. Serna, W. Qiang, D. C. Brooks, S. S. Malpani, et al. (2013)
PNAS 110, 17053-17058
   Abstract »    Full Text »    PDF »
Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and -9 in human uterine fibroid cells.
S. K. Halder, K. G. Osteen, and A. Al-Hendy (2013)
Hum. Reprod. 28, 2407-2416
   Abstract »    Full Text »    PDF »
Loss of the repressor REST in uterine fibroids promotes aberrant G protein-coupled receptor 10 expression and activates mammalian target of rapamycin pathway.
B. V. Varghese, F. Koohestani, M. McWilliams, A. Colvin, S. Gunewardena, W. H. Kinsey, R. A. Nowak, W. B. Nothnick, and V. M. Chennathukuzhi (2013)
PNAS 110, 2187-2192
   Abstract »    Full Text »    PDF »
Validation of the Aging Hen (Gallus gallus domesticus) as an Animal Model for Uterine Leiomyomas.
S. A. Machado, J. M. Bahr, D. B. Hales, A. G. Braundmeier, B. J. Quade, and R. A. Nowak (2012)
Biol Reprod 87, 86
   Abstract »    Full Text »    PDF »
miR-200c is aberrantly expressed in leiomyomas in an ethnic-dependent manner and targets ZEBs, VEGFA, TIMP2, and FBLN5.
T.-D. Chuang, H. Panda, X. Luo, and N. Chegini (2012)
Endocr. Relat. Cancer 19, 541-556
   Abstract »    Full Text »    PDF »
The Endothelin Axis in Uterine Leiomyomas: New Insights.
Z. Tanfin and M. Breuiller-Fouche (2012)
Biol Reprod 87, 5
   Abstract »    Full Text »    PDF »
Environmental Estrogens Differentially Engage the Histone Methyltransferase EZH2 to Increase Risk of Uterine Tumorigenesis.
K. L. Greathouse, T. Bredfeldt, J. I. Everitt, K. Lin, T. Berry, K. Kannan, M. L. Mittelstadt, S.-m. Ho, and C. L. Walker (2012)
Mol. Cancer Res. 10, 546-557
   Abstract »    Full Text »    PDF »
1,25-Dihydroxyvitamin D3 Treatment Shrinks Uterine Leiomyoma Tumors in the Eker Rat Model.
S. K. Halder, C. Sharan, and A. Al-Hendy (2012)
Biol Reprod 86, 116
   Abstract »    Full Text »    PDF »
Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications.
P. Ciarmela, M. S. Islam, F. M. Reis, P. C. Gray, E. Bloise, F. Petraglia, W. Vale, and M. Castellucci (2011)
Hum. Reprod. Update 17, 772-790
   Abstract »    Full Text »    PDF »
Histone Deacetylase 6 Regulates Estrogen Receptor {alpha} in Uterine Leiomyoma.
L.-H. Wei, P.-L. Torng, S.-M. Hsiao, Y.-M. Jeng, M.-W. Chen, and C.-A. Chen (2011)
Reproductive Sciences 18, 755-762
   Abstract »    Full Text »    PDF »
MAPK14 Cooperates with MAPK3/1 to Regulate Endothelin-1-Mediated Prostaglandin Synthase 2 Induction and Survival in Leiomyoma but Not in Normal Myometrial Cells.
C. Oyeniran and Z. Tanfin (2011)
Biol Reprod 84, 495-504
   Abstract »    Full Text »    PDF »
Characteristics indicating adenomyosis coexisting with leiomyomas: a case-control study.
F. A. Taran, A. L. Weaver, C. C. Coddington, and E. A. Stewart (2010)
Hum. Reprod. 25, 1177-1182
   Abstract »    Full Text »    PDF »
Reactive Oxygen Species Mediate Mitogenic Growth Factor Signaling Pathways in Human Leiomyoma Smooth Muscle Cells.
F. S. Mesquita, S. N. Dyer, D. A. Heinrich, S. E. Bulun, E. E. Marsh, and R. A. Nowak (2010)
Biol Reprod 82, 341-351
   Abstract »    Full Text »    PDF »
Platelet-Derived Growth Factor C Is Upregulated in Human Uterine Fibroids and Regulates Uterine Smooth Muscle Cell Growth.
G. Suo, Y. Jiang, B. Cowan, and J. Y.J. Wang (2009)
Biol Reprod 81, 749-758
   Abstract »    Full Text »    PDF »
Constitutive Activation of Beta-Catenin in Uterine Stroma and Smooth Muscle Leads to the Development of Mesenchymal Tumors in Mice.
P. S. Tanwar, H.-J. Lee, L. Zhang, L. R. Zukerberg, M. M. Taketo, B. R. Rueda, and J. M. Teixeira (2009)
Biol Reprod 81, 545-552
   Abstract »    Full Text »    PDF »
Comparison of Human and Rat Uterine Leiomyomata: Identification of a Dysregulated Mammalian Target of Rapamycin Pathway.
J. S. Crabtree, S. A. Jelinsky, H. A. Harris, S. E. Choe, M. M. Cotreau, M. L. Kimberland, E. Wilson, K. A. Saraf, W. Liu, A. S. McCampbell, et al. (2009)
Cancer Res. 69, 6171-6178
   Abstract »    Full Text »    PDF »
Identification of Uterine Leiomyoma Genes Developmentally Reprogrammed by Neonatal Exposure to Diethylstilbestrol.
K.L. Greathouse, J.D. Cook, K. Lin, B.J. Davis, T.D. Berry, T.G. Bredfeldt, and C.L. Walker (2008)
Reproductive Sciences 15, 765-778
   Abstract »    PDF »
A low concentration of genistein induces estrogen receptor-alpha and insulin-like growth factor-I receptor interactions and proliferation in uterine leiomyoma cells.
X. Di, L. Yu, A.B. Moore, L. Castro, X. Zheng, T. Hermon, and D. Dixon (2008)
Hum. Reprod. 23, 1873-1883
   Abstract »    Full Text »    PDF »
Retinoids regulate genes involved in retinoic acid synthesis and transport in human myometrial and fibroid smooth muscle cells.
M. Zaitseva, B. J. Vollenhoven, and P. A.W. Rogers (2008)
Hum. Reprod. 23, 1076-1086
   Abstract »    Full Text »    PDF »
Progesterone receptor modulator CDB-2914 induces extracellular matrix metalloproteinase inducer in cultured human uterine leiomyoma cells.
Q. Xu, N. Ohara, J. Liu, M. Amano, R. Sitruk-Ware, S. Yoshida, and T. Maruo (2008)
Mol. Hum. Reprod. 14, 181-191
   Abstract »    Full Text »    PDF »
Hysteroscopic myomectomy: a comprehensive review of surgical techniques.
A. Di Spiezio Sardo, I. Mazzon, S. Bramante, S. Bettocchi, G. Bifulco, M. Guida, and C. Nappi (2008)
Hum. Reprod. Update 14, 101-119
   Abstract »    Full Text »    PDF »
Role of lysophosphatidic acid in the regulation of uterine leiomyoma cell proliferation by phospholipase D and autotaxin.
E. Billon-Denis, Z. Tanfin, and P. Robin (2008)
J. Lipid Res. 49, 295-307
   Abstract »    Full Text »    PDF »
Dual repressive effect of angiotensin II-type 1 receptor blocker telmisartan on angiotensin II-induced and estradiol-induced uterine leiomyoma cell proliferation.
A. Isobe, T. Takeda, M. Sakata, A. Miyake, T. Yamamoto, R. Minekawa, F. Nishimoto, Y. Oskamoto, C. L. Walker, and T. Kimura (2008)
Hum. Reprod. 23, 440-446
   Abstract »    Full Text »    PDF »
Thrombospondin-1 and Thrombospondin-2 mRNA and TSP-1 and TSP-2 Protein Expression in Uterine Fibroids and Correlation to the Genes COL1A1 and COL3A1 and to the Collagen Cross-link Hydroxyproline.
M. A. Behera, L. Feng, B. Yonish, W. Catherino, S.-H. Jung, and P. C. Leppert (2007)
Reproductive Sciences 14, 63-76
   Abstract »    PDF »
Side population in human uterine myometrium displays phenotypic and functional characteristics of myometrial stem cells.
M. Ono, T. Maruyama, H. Masuda, T. Kajitani, T. Nagashima, T. Arase, M. Ito, K. Ohta, H. Uchida, H. Asada, et al. (2007)
PNAS 104, 18700-18705
   Abstract »    Full Text »    PDF »
Tumor-Specific Efficacy of Transforming Growth Factor-{beta}RI Inhibition in Eker Rats.
N. J. Laping, J. I. Everitt, K. S. Frazier, M. Burgert, M. J. Portis, C. Cadacio, L. I. Gold, and C. L. Walker (2007)
Clin. Cancer Res. 13, 3087-3099
   Abstract »    Full Text »    PDF »
Invited Comment: "Identification of a Sensitive Period for Developmental Programming That Increases Risk for Uterine Leiomyoma in Eker Rats".
J. H. Segars (2007)
Reproductive Sciences 14, 99-100
   PDF »
Absolute enrichment: gene set enrichment analysis for homeostatic systems.
V. Saxena, D. Orgill, and I. Kohane (2006)
Nucleic Acids Res. 34, e151
   Abstract »    Full Text »    PDF »
Estrogen Metabolite 2-Methoxyestradiol Induces Apoptosis and Inhibits Cell Proliferation and Collagen Production in Rat and Human Leiomyoma Cells: A Potential Medicinal Treatment for Uterine Fibroids.
S. A. Salama, A. B. Nasr, R. K. Dubey, and A. Al-Hendy (2006)
Reproductive Sciences 13, 542-550
   Abstract »    PDF »
Gene therapy and uterine leiomyoma: a review.
A. Al-Hendy and S. Salama (2006)
Hum. Reprod. Update 12, 385-400
   Abstract »    Full Text »    PDF »
In vitro culture significantly alters gene expression profiles and reduces differences between myometrial and fibroid smooth muscle cells.
M. Zaitseva, B. J. Vollenhoven, and P. A.W. Rogers (2006)
Mol. Hum. Reprod. 12, 187-207
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882