Insights from Gene Arrays on the Development and Growth Regulation of Uterine Leiomyomata

Overview

Journal Fertil Steril

Specialty Reproductive Medicine

Date 2002 Jul 4

PMID 12095500

Citations 47

Authors

John C M Tsibris

James Segars

Domenico Coppola

Shrikant Mane

George D Wilbanks

William F OBrien

William N Spellacy

Affiliations

Soon will be listed here.

Abstract

Objective: To use microarray analysis as an unbiased approach to identify genes involved in the induction and growth of uterine leiomyomata.

Design: Screen by arrays for up to 12,000 genes in leiomyoma (L) and control myometrium (M) from nine patients.

Setting: University research laboratories.

Patient(s): Nine patients in the follicular and luteal phases of the menstrual cycle.

Intervention(s): mRNA from L and M was converted to biotin-labeled cRNA and hybridized to cDNA oligonucleotide sequences on the arrays.

Main Outcome Measure(s): Greater than two-fold change in gene expression between leiomyoma and matched myometrium.

Result(s): Prominent among the 67 genes overexpressed in L relative to M were dlk or Pref-1, doublecortin, JM27, ionotropic glutamate receptor subunit 2, apolipoprotein E3, IGF2, semaphorin F, myelin proteolipid protein, MEST, frizzled, CRABP II, stromelysin-3, and TGFbeta3. The genes dlk, IGF2, and MEST are paternally expressed imprinted genes, and the others are involved in tissue differentiation and growth. Prominent among the 78 genes down-regulated in L relative to M were alcohol dehydrogenases 1alpha-gamma, tryptase, dermatopontin, thrombospondin, coxsackievirus receptor, nur77, and c-kit.

Conclusion(s): Arrays offer large-scale screening of mRNA expression, which will help us differentiate between the genes and metabolic pathways necessary for leiomyoma growth and those regulating myometrial contractions.

Citing Articles

BCL6 (B-cell lymphoma 6) expression in adenomyosis, leiomyomas and normal myometrium.

Salas L, Mielczarski B, Rivero R, da Cunha Filho J, Savaris R PLoS One. 2025; 20(2):e0317136.

PMID: 39903727 PMC: 11793761. DOI: 10.1371/journal.pone.0317136.

Transcriptome profiling reveals dysregulation of inflammatory and protein synthesis genes in PCOS.

Li X, Gao B, Gao B, Li X, Xia X Sci Rep. 2024; 14(1):16596.

PMID: 39025980 PMC: 11258128. DOI: 10.1038/s41598-024-67461-4.

Non-collagenous extracellular matrix protein dermatopontin may play a role as another component of transforming growth factor-β signaling pathway in colon carcinogenesis.

Sadr-Nabavi A, Bouromand-Noughabi S, Tayebi-Meybodi N, Dadkhah K, Amini N, Meindl A Iran J Basic Med Sci. 2021; 24(4):444-450.

PMID: 34094025 PMC: 8143710. DOI: 10.22038/IJBMS.2021.46422.10720.

Evidence of biomechanical and collagen heterogeneity in uterine fibroids.

Jayes F, Liu B, Feng L, Aviles-Espinoza N, Leikin S, Leppert P PLoS One. 2019; 14(4):e0215646.

PMID: 31034494 PMC: 6488189. DOI: 10.1371/journal.pone.0215646.

Regulation of Cell Cycle Regulatory Proteins by MicroRNAs in Uterine Leiomyoma.

Chuang T, Khorram O Reprod Sci. 2018; 26(2):250-258.

PMID: 29642801 PMC: 6728566. DOI: 10.1177/1933719118768692.

References

Palomba S, Sammartino A, Di Carlo C, Affinito P, Zullo F, Nappi C . Effects of raloxifene treatment on uterine leiomyomas in postmenopausal women. Fertil Steril. 2001; 76(1):38-43. DOI: 10.1016/s0015-0282(01)01849-0. View

Takemori H, Doi J, Katoh Y, Halder S, Lin X, Horike N . Characterization of a proximal element in the rat preadipocyte factor-1 (Pref-1) gene promoter. Eur J Biochem. 2001; 268(2):205-17. DOI: 10.1046/j.1432-1033.2001.01847.x. View

Marshall L, Spiegelman D, Manson J, Goldman M, Barbieri R, Stampfer M . Risk of uterine leiomyomata among premenopausal women in relation to body size and cigarette smoking. Epidemiology. 1998; 9(5):511-7. View

Cohen C, Shieh J, Pickles R, Okegawa T, Hsieh J, Bergelson J . The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction. Proc Natl Acad Sci U S A. 2001; 98(26):15191-6. PMC: 65005. DOI: 10.1073/pnas.261452898. View

Parrott E, Butterworth M, Green A, White I, Greaves P . Adenomyosis--a result of disordered stromal differentiation. Am J Pathol. 2001; 159(2):623-30. PMC: 1850567. DOI: 10.1016/S0002-9440(10)61733-6. View

Rudolph M, Reinicke K, Cruz M, Gallardo V, Gonzalez C, BARDISA L . Distribution of mast cells and the effect of their mediators on contractility in human myometrium. Br J Obstet Gynaecol. 1993; 100(12):1125-30. DOI: 10.1111/j.1471-0528.1993.tb15178.x. View

Mauro L, Salerno M, Panno M, Bellizzi D, Sisci D, Miglietta A . Estradiol increases IRS-1 gene expression and insulin signaling in breast cancer cells. Biochem Biophys Res Commun. 2001; 288(3):685-9. DOI: 10.1006/bbrc.2001.5815. View

Fajas L, Debril M, Auwerx J . Peroxisome proliferator-activated receptor-gamma: from adipogenesis to carcinogenesis. J Mol Endocrinol. 2001; 27(1):1-9. DOI: 10.1677/jme.0.0270001. View

Vu K, Greenspan D, Wu T, Zacur H, Kurman R . Cellular proliferation, estrogen receptor, progesterone receptor, and bcl-2 expression in GnRH agonist-treated uterine leiomyomas. Hum Pathol. 1998; 29(4):359-63. DOI: 10.1016/s0046-8177(98)90116-2. View

10.

Wang H, Wu X, Englund K, Masironi B, Eriksson H, Sahlin L . Different expression of estrogen receptors alpha and beta in human myometrium and leiomyoma during the proliferative phase of the menstrual cycle and after GnRHa treatment. Gynecol Endocrinol. 2002; 15(6):443-52. View

11.

Ohno N, Izawa A, Hattori M, Kageyama R, Sudo T . dlk inhibits stem cell factor-induced colony formation of murine hematopoietic progenitors: Hes-1-independent effect. Stem Cells. 2001; 19(1):71-9. DOI: 10.1634/stemcells.19-1-71. View

12.

Vu T, Yballe C, Boonyanit S, Hoffman A . Insulin-like growth factor II in uterine smooth-muscle tumors: maintenance of genomic imprinting in leiomyomata and loss of imprinting in leiomyosarcomata. J Clin Endocrinol Metab. 1995; 80(5):1670-6. DOI: 10.1210/jcem.80.5.7745016. View

13.

Perou C, Sorlie T, Eisen M, van de Rijn M, Jeffrey S, Rees C . Molecular portraits of human breast tumours. Nature. 2000; 406(6797):747-52. DOI: 10.1038/35021093. View

14.

Wu T . Analysing gene expression data from DNA microarrays to identify candidate genes. J Pathol. 2001; 195(1):53-65. DOI: 10.1002/1096-9896(200109)195:1<53::AID-PATH891>3.0.CO;2-H. View

15.

Faerstein E, Szklo M, Rosenshein N . Risk factors for uterine leiomyoma: a practice-based case-control study. I. African-American heritage, reproductive history, body size, and smoking. Am J Epidemiol. 2001; 153(1):1-10. DOI: 10.1093/aje/153.1.1. View

16.

Gross K, Morton C . Genetics and the development of fibroids. Clin Obstet Gynecol. 2001; 44(2):335-49. DOI: 10.1097/00003081-200106000-00020. View

17.

Saito H, Nakajima T, Matsumoto K . Human mast cell transcriptome project. Int Arch Allergy Immunol. 2001; 125(1):1-8. DOI: 10.1159/000053790. View

18.

Cuisset L, Le Stunff C, Dupont J, Vasseur C, Cartigny M, Despert F . PEG1 expression in maternal uniparental disomy 7. Ann Genet. 1997; 40(4):211-5. View

19.

Maas S, Patt S, Schrey M, Rich A . Underediting of glutamate receptor GluR-B mRNA in malignant gliomas. Proc Natl Acad Sci U S A. 2001; 98(25):14687-92. PMC: 64742. DOI: 10.1073/pnas.251531398. View

20.

Rainho C, Pontes A, Rogatto S . Expression and imprinting of insulin-like growth factor II (IGF2) and H19 genes in uterine leiomyomas. Gynecol Oncol. 1999; 74(3):375-80. DOI: 10.1006/gyno.1999.5483. View