Download PDF
Semin Reprod Med 2004; 22(2): 91-103
DOI: 10.1055/s-2004-828615
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Apoptosis in Human Uterine Leiomyomas

Kristina M. Martel1 , Angela C. Ko2 , Gregory M. Christman2 , John M. Stribley2 , 3
  • 1University of Michigan Medical School, Ann Arbor, Michigan
  • 2Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, Michigan
  • 3Division of Anatomical Sciences, University of Michigan Medical School, Ann Arbor, Michigan
Further Information

Publication History

Publication Date:
26 May 2004 (online)

    Permissions and Reprints

Human uterine leiomyomas (fibroids) are benign neoplasms that typically occur in reproductive age and perimenopausal women. These tumors pose a significant and costly health concern for numerous women throughout the world. Alternative therapies are few, with hysterectomy being the treatment of choice by many physicians. There is a growing body of evidence suggesting that the development of leiomyomas may be influenced by numerous factors including genetic, environmental, and hormonal influences resulting in a possible failure of any number of apoptotic pathways. Understanding the role apoptosis plays in the normal regression of nascent myometrial tissue and how this failure may influence leiomyoma tumor growth may provide a better understanding of how to develop effective and less invasive treatment modalities for this disease. The following review attempts to highlight what is currently known about apoptosis in leiomyomas as compared with the normal myometrium and where future research is needed.

KEYWORDS

Leiomyomas - uterus - fibroids - apoptosis

REFERENCES

  • 1 Wilcox L S, Koonin L M, Pokras R, Strauss L T, Xia Z, Peterson H B. Hysterectomy in the United States, 1988-1990.  Obstet Gynecol. 1994;  83 549-555
    CrossrefPubMedGoogle Scholar
  • 2 Marshall L M, Spiegelman D, Barbieri R L et al.. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race.  Obstet Gynecol. 1997;  90 967-973
    CrossrefPubMedGoogle Scholar
  • 3 Ross R K, Pike M C, Vessey M P, Bull D, Yeates D, Casagrande J T. Risk factors for uterine fibroids: reduced risk associated with oral contraceptives.  Br Med J (Clin Res Ed). 1986;  293 359-362
    PubMedGoogle Scholar
  • 4 Schwartz S M. Epidemiology of uterine leiomyomata.  Clin Obstet Gynecol. 2001;  44 316-326
    CrossrefPubMedGoogle Scholar
  • 5 Garcia Muret M P, Pujol R M, Alomar A, Calaf J, de Moragas J M. Familial leiomyomatosis cutis et uteri (Reed's syndrome).  Arch Dermatol Res. 1988;  280(suppl) S29-S32
    CrossrefPubMedGoogle Scholar
  • 6 Kjerulff K H, Guzinski G M, Langenberg P W, Stolley P D, Moye N E, Kazandjian V A. Hysterectomy and race.  Obstet Gynecol. 1993;  82 757-764
    PubMedGoogle Scholar
  • 7 Treloar S A, Do K A, O'Connor V M, O'Connor D T, Yeo M A, Martin N G. Predictors of hysterectomy: an Australian study.  Am J Obstet Gynecol. 1999;  180 945-954
    PubMedGoogle Scholar
  • 8 Schwartz S M, Marshall L M, Baird D D. Epidemiologic contributions to understanding the etiology of uterine leiomyomata.  Environ Health Perspect. 2000;  108(suppl 5) 821-827
    CrossrefPubMedGoogle Scholar
  • 9 Chavez N F, Stewart E A. Medical treatment of uterine fibroids.  Clin Obstet Gynecol. 2001;  44 372-384
    CrossrefPubMedGoogle Scholar
  • 10 Walker C L, Burroughs K D, Davis B, Sowell K, Everitt J I, Fuchs-Young R. Preclinical evidence for therapeutic efficacy of selective estrogen receptor modulators for uterine leiomyoma.  J Soc Gynecol Investig. 2000;  7 249-256
    PubMedGoogle Scholar
  • 11 Matsuo H, Maruo T, Samoto T. Increased expression of Bcl-2 protein in human uterine leiomyoma and its up-regulation by progesterone.  J Clin Endocrinol Metab. 1997;  82 293-299
    CrossrefPubMedGoogle Scholar
  • 12 Dixon D, Flake G P, Moore A B et al.. Cell proliferation and apoptosis in human uterine leiomyomas and myometria.  Virchows Arch. 2002;  441 53-62
    CrossrefPubMedGoogle Scholar
  • 13 Wu X, Blanck A, Olovsson M, Henriksen R, Lindblom B. Expression of Bcl-2, Bcl-x, Mcl-1, Bax and Bak in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause.  J Steroid Biochem Mol Biol. 2002;  80 77-83
    CrossrefPubMedGoogle Scholar
  • 14 Vu K, Greenspan D L, Wu T C, Zacur H A, Kurman R J. Cellular proliferation, estrogen receptor, progesterone receptor, and bcl-2 expression in GnRH agonist-treated uterine leiomyomas.  Hum Pathol. 1998;  29 359-363
    CrossrefPubMedGoogle Scholar
  • 15 Wang Y, Matsuo H, Kurachi O, Maruo T. Down-regulation of proliferation and up-regulation of apoptosis by gonadotropin-releasing hormone agonist in cultured uterine leiomyoma cells.  Eur J Endocrinol. 2002;  146 447-456
    CrossrefPubMedGoogle Scholar
  • 16 Matsuo H, Kurachi O, Shimomura Y, Samoto T, Maruo T. Molecular bases for the actions of ovarian sex steroids in the regulation of proliferation and apoptosis of human uterine leiomyoma.  Oncology. 1999;  57(suppl 2) 49-58
    PubMedGoogle Scholar
  • 17 Huang S C, Tang M J, Hsu K F, Cheng Y M, Chou C Y. Fas and its ligand, caspases, and bcl-2 expression in gonadotropin-releasing hormone agonist-treated uterine leiomyoma.  J Clin Endocrinol Metab. 2002;  87 4580-4586
    CrossrefPubMedGoogle Scholar
  • 18 Sedlak T W, Oltvai Z N, Yang E et al.. Multiple Bcl-2 family members demonstrate selective dimerizations with Bax.  Proc Natl Acad Sci U S A. 1995;  92 7834-7838
    PubMedGoogle Scholar
  • 19 Gao Z, Matsuo H, Nakago S, Kurachi O, Maruo T. p53 tumor suppressor protein content in human uterine leiomyomas and its down-regulation by 17 beta-estradiol.  J Clin Endocrinol Metab. 2002;  87 3915-3920
    CrossrefPubMedGoogle Scholar
  • 20 Wu X, Blanck A, Olovsson M, Moller B, Favini R, Lindblom B. Apoptosis, cellular proliferation and expression of p53 in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause.  Acta Obstet Gynecol Scand. 2000;  79 397-404
    CrossrefPubMedGoogle Scholar
  • 21 Baek W K, Kim D, Jung N et al.. Increased expression of cyclin G1 in leiomyoma compared with normal myometrium.  Am J Obstet Gynecol. 2003;  188 634-639
    CrossrefPubMedGoogle Scholar
  • 22 Gupta S. Molecular signaling in death receptor and mitochondrial pathways of apoptosis (review).  Int J Oncol. 2003;  22 15-20
    PubMedGoogle Scholar
  • 23 Haviv R, Stein R. Nerve growth factor inhibits apoptosis induced by tumor necrosis factor in PC12 cells.  J Neurosci Res. 1999;  55 269-277
    CrossrefPubMedGoogle Scholar
  • 24 Kurachi O, Matsuo H, Samoto T, Maruo T. Tumor necrosis factor-alpha expression in human uterine leiomyoma and its down-regulation by progesterone.  J Clin Endocrinol Metab. 2001;  86 2275-2280
    CrossrefPubMedGoogle Scholar
  • 25 Gao Z, Matsuo H, Wang Y, Nakago S, Maruo T. Up-regulation by IGF-I of proliferating cell nuclear antigen and Bcl-2 protein expression in human uterine leiomyoma cells.  J Clin Endocrinol Metab. 2001;  86 5593-5599
    CrossrefPubMedGoogle Scholar
  • 26 Huang J, Zou J, Xu B, Zhang Y, Chen X, Liu D. [Affect of insulin-like growth factor I and estradiol on the growth of uterine leiomyoma].  Hunan Yi Ke Da Xue Xue Bao. 1999;  24 29-32
    PubMedGoogle Scholar
  • 27 Gerdes J, Li L, Schlueter C et al.. Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67.  Am J Pathol. 1991;  138 867-873
    PubMedGoogle Scholar
  • 28 Englund K, Lindblom B, Carlstrom K, Gustavsson I, Sjoblom P, Blanck A. Gene expression and tissue concentrations of IGF-I in human myometrium and fibroids under different hormonal conditions.  Mol Hum Reprod. 2000;  6 915-920
    CrossrefPubMedGoogle Scholar
  • 29 Mizutani T, Sugihara A, Nakamuro K, Terada N. Suppression of cell proliferation and induction of apoptosis in uterine leiomyoma by gonadotropin-releasing hormone agonist (leuprolide acetate).  J Clin Endocrinol Metab. 1998;  83 1253-1255
    CrossrefPubMedGoogle Scholar
  • 30 Shimomura Y, Matsuo H, Samoto T, Maruo T. Up-regulation by progesterone of proliferating cell nuclear antigen and epidermal growth factor expression in human uterine leiomyoma.  J Clin Endocrinol Metab. 1998;  83 2192-2198
    CrossrefPubMedGoogle Scholar
  • 31 Maruo T, Matsuo H, Samoto T et al.. Effects of progesterone on uterine leiomyoma growth and apoptosis.  Steroids. 2000;  65 585-592
    CrossrefPubMedGoogle Scholar

John M StribleyPh.D. 

1150 West Medical Center Drive, Medical Science I

Room 6422, Ann Arbor, MI 48109-0617