ArticleMolecular endocrinology (Baltimore, Md.)2013
Uterine-specific loss of Tsc2 leads to myometrial tumors in both the uterus and lungs.
Article in Molecular endocrinology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03500367 (Efficacy and Safety of Rapamycin), which is not on this map. Cited by 43 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Efficacy and Safety of Rapamycin (Sirolimus) in the Treatment of Symptomatic Uterine Fibroids and Leiomyomatosis
Who cites it
43 citing papers in PubMed, 63 citations in OpenAlex.
- Current insight into the molecular mechanisms of lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2026Review
- Intersecting Roles of Estrogens and Neutrophils in Modulating Innate Immunity in Cancer.Biomolecules · 2026Review
- Preclinical research platform for uterine leiomyoma: construction optimization and selection of animal models.Frontiers in veterinary science · 2026Article
- Extracellular vesicles modulate integrin signaling and subcellular energetics to promote pulmonary lymphangioleiomyomatosis metastasis.Communications biology · 2025Article
- Multifocal micronodular pneumocyte hyperplasia and splenic hamartomas in tuberous sclerosis complex: A case report.Radiology case reports · 2025Article
- Inflammatory, Functional, and Compositional Changes of the Uterine Immune Microenvironment in a Lymphangioleiomyomatosis Mouse Model.Journal of cellular immunology · 2025Article
- STAT1 Promotes PD-L1 Activation and Tumor Growth in Lymphangioleiomyomatosis.bioRxiv : the preprint server for biology · 2024Article
- Establishment of 3D Cultures of Myometrium, Leiomyoma, and Leiomyosarcoma Cells: Advantages and Disadvantages of Two Different Models.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Lymphangioleiomyomatosis and pregnancy: a mini-review.Archives of gynecology and obstetrics · 2024Review
- Malignant tumors in tuberous sclerosis complex: a case report and review of the literature.BMC medical genomics · 2024Review
- A Case Report of Malignant Perivascular Epithelioid Cell Tumors of the Uterus and Literature Review.International journal of women's health · 2024Article
- Lymphangioleiomyomatosis: where endocrinology, immunology and tumor biology meet.Endocrine-related cancer · 2023Review
- Single-cell multiomic analysis identifies a HOX-PBX gene network regulating the survival of lymphangioleiomyomatosis cells.Science advances · 2023Article
- Lymphangioleiomyomatosis and Other Cystic Lung Diseases.Immunology and allergy clinics of North America · 2023Review
- Estradiol Augments Tumor-Induced Neutrophil Production to Promote Tumor Cell Actions in Lymphangioleiomyomatosis Models.Endocrinology · 2023Article
- Single-cell sequencing reveals novel cellular heterogeneity in uterine leiomyomas.Human reproduction (Oxford, England) · 2022Article
- Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment.Endocrine reviews · 2022Review
- Evidence for shared genetic risk factors between lymphangioleiomyomatosis and pulmonary function.ERJ open research · 2022Article
- Acute and repeated haemoperitoneum: a challenging case of lymphangioleiomyomatosis with uterine PEComa.BMJ case reports · 2021Article
- Tuberous sclerosis complex for the pulmonologist.European respiratory review : an official journal of the European Respiratory Society · 2021Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Lymphangioleiomyomatosis (LAM) is a rare disease characterized by proliferation of abnormal smooth-muscle cells in the lungs, leading to functional loss and sometimes lung transplantation. Although the origin of LAM cells is unknown, several features of LAM provide clues. First, LAM cells contain inactivating mutations in genes encoding Tsc1 or Tsc2, proteins that limit mTORC1 activity. Second, LAM tumors recur after lung transplantation, suggesting a metastatic pathogenesis. Third, LAM is found almost exclusively in women. Finally, LAM shares features with uterine leiomyomas, benign tumors of myometrial cells. From these observations, we proposed that LAM cells might originate from uterine leiomyomas containing Tsc mutations. To test our hypothesis, and to develop mouse models for leiomyoma and LAM, we targeted Tsc2 deletion primarily in uterine cells. In fact, nearly 100% of uteri from uterine-specific Tsc2 knockout mice developed myometrial proliferation and uterine leiomyomas by 12 and 24 weeks, respectively. Myometrial proliferation and mTORC1/S6 activity were abrogated by the mTORC1 inhibitor rapamycin or by elimination of sex steroid production through ovariectomy or aromatase inhibition. In ovariectomized Tsc2 null mice, mTORC1/S6 activity and myometrial growth were restored by estrogen but not progesterone. Thus, even without Tsc2, estrogen appears to be required for myometrial mTORC1/S6 signaling and proliferation. Finally, we found Tsc2 null myometrial tumors in lungs of older Tsc2 uterine-specific knockout females, suggesting that lung LAM-like myometrial lesions may indeed originate from the uterus. This mouse model may improve our understanding of LAM and leiomyomas and might lead to novel therapeutic strategies for both diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.