A new hypothesis about the origin of uterine fibroids based on gene expression profiling with microarrays

Leppert, Phyllis C.; Catherino, William H.; Segars, James H.

doi:10.1016/j.ajog.2005.12.059

Cited by 163 publications

(173 citation statements)

References 35 publications

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“…This hypothesis was discussed as early as the 1930s, 29 but has never been carefully tested. 12 Recent suggestions that fibroid pathogenesis mimicks abnormal wound healing, 30 and possible involvement of inflammation 31 provides impetus for trying to carefully evaluate this hypothesis.…”

Section: Methodsmentioning

confidence: 99%

A Prospective, Ultrasound-Based Study to Evaluate Risk Factors for Uterine Fibroid Incidence and Growth: Methods and Results of Recruitment

Baird

Harmon

Upson

et al. 2015

Journal of Women's Health

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Background: Uterine fibroids are common, benign, smooth-muscle tumors that can cause major morbidity for reproductive-age women, often requiring invasive treatment. Despite this personal and public health burden, no prior study has attempted to periodically screen fibroid-free women with ultrasound to detect incident disease and identify risk factors. Methods: We designed a study to prospectively investigate development of fibroids by enrolling women without a clinical diagnosis of fibroids and screening for fibroids with ultrasound at baseline. Enrollment procedures included extensive questionnaires and specimen collection (blood, urine, vaginal swabs). The cohort is followed at approximately 20-month intervals. At each follow-up there are updates to the questionnaire data, further specimen collection, and an ultrasound examination. We identify incident disease and measure tumor growth. The two exposures of primary interest are vitamin D insufficiency and reproductive tract infections. This manuscript provides a detailed description of the study methods, recruitment results, and participant characteristics. Results: The Study of Environment, Lifestyle and Fibroids enrolled 1,696 African American women aged 23-34 years. ''Family and friends'' was a leading recruitment source. More than 95% of participants contributed all the requested biological specimens at baseline. Study ultrasound examinations revealed undiagnosed fibroids in 378 women (22% of participants). The retention rate for the first follow-up was 87%. Conclusions: Study design aspects likely to be important for long-term studies in young African Americans include personalized recruitment, multiple steps to the enrollment process that rely on the initiative of the participant, and methods for tracing highly mobile study subjects.

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Section: Methodsmentioning

confidence: 99%

A Prospective, Ultrasound-Based Study to Evaluate Risk Factors for Uterine Fibroid Incidence and Growth: Methods and Results of Recruitment

Baird

Harmon

Upson

et al. 2015

Journal of Women's Health

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“…[12][13][14][15][16] Our previous studies of uterine fibroids using microarrays have served to focus attention on the ECM of uterine fibroids and the similarity of fibroids to tissue remodeling and repair. 34 We noted that fibroids were composed of an ECM with altered organization of structural elements, such as collagen fibers.18 In addition, we17 and others12,15,35 have noted that fibroid express altered levels of key proteoglycans, such as dermatopontin and versican. The current study supports and extends upon the notion of altered tissue repair, because formation of a load-bearing ECM is a key step in tissue repair.…”

Section: Commentmentioning

confidence: 99%

Mechanical homeostasis is altered in uterine leiomyoma

Rogers

Norian

Malik

et al. 2008

American Journal of Obstetrics and Gynecology

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109

120

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Objective-Uterine leiomyoma produce an extracellular matrix (ECM) that is abnormal in its volume, content, and structure. Alterations in ECM can modify mechanical stress on cells, leading to activation of Rho-dependent signaling. Here we sought to determine whether the altered ECM produced by leiomyoma was accompanied by an altered state of mechanical homeostasis.Study Design-Measurement of the mechanical response in paired leiomyoma and myometrium, immunogold, confocal microscopy, and immunohistochemical analyses.Results-Leiomyoma were significantly stiffer than matched myometrium. The increased stiffness was associated with a moderate increase in total sulfated glycosaminoglycan content and a slight increase in hydroxyproline. Levels of the Rho-GEF, AKAP13, were increased and subcellular localization was altered in leiomyoma. Phosphorylation of p38MAPK was greater in leiomyoma extracts. Conclusions-Leiomyoma

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“…Furthermore, a review of gene expression data revealed concordant changes in the genes regulating retinoid synthesis, insulin-like growth factor metabolism, transforming growth factor signaling and extracellular matrix formation (7). A larger scale gene expression analysis also contributed to a better understanding of UL (8). However, the biology of UL remains obscure.…”

Section: Introductionmentioning

confidence: 99%

SPARC-like1 mRNA is overexpressed in human uterine leiomyoma

Mencalha

Levinsphul²,

Deterling³

et al. 2008

Mol Med Report

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Abstract. Uterine leiomyomas (ULs), also known as fibroids, are benign and monoclonal tumors frequently found in the female population. The genetic alterations that contribute to UL tumor development have not been well established, and the goal of this study was to reveal gene expression variation between ULs and healthy uterine tissue. We compared the gene expression profiles of 13 UL tumors with that of their adjacent normal tissue using the Differential Display mRNA assay (DDRT-PCR). Among the genes upregulated in some of the UL samples, several genes previously described in the context of cancer were identified, namely LIMK1, MCM3 and UHRF1. In addition, we identified a cDNA present in UL samples from distinct patients, which was absent from their normal tissue. Direct sequencing of this cDNA revealed a human SPARC-like1 (SPARCL1) mRNA homology. Through semi-quantitative PCR, we demonstrated that SPARCL1 was upregulated in approximately 77% of UL samples, but was absent in normal tissue. Real-time PCR (QPCR) revealed that SPARCL1 expression was increased 5-fold in ULs compared to adjacent normal tissue. These results suggest that the SPARCL1 gene is involved in UL development.

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A new hypothesis about the origin of uterine fibroids based on gene expression profiling with microarrays

Cited by 163 publications

References 35 publications

A Prospective, Ultrasound-Based Study to Evaluate Risk Factors for Uterine Fibroid Incidence and Growth: Methods and Results of Recruitment

A Prospective, Ultrasound-Based Study to Evaluate Risk Factors for Uterine Fibroid Incidence and Growth: Methods and Results of Recruitment

Mechanical homeostasis is altered in uterine leiomyoma

SPARC-like1 mRNA is overexpressed in human uterine leiomyoma

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