title: Intracrine steroid production and mammalian target of rapamycin pathways in pulmonary lymphangioleiomyomatosis.
abstract: Lymphangioleiomyomatosis (LAM) is a rare, potentially fatal disease primarily affecting young women. Estrogens enhance cell proliferation and progression of the tumor. Clinical trials using molecularly targeted agents such as endocrine manipulation and mammalian target of rapamycin (mTOR) inhibitors are in progress, but the status of these molecules, including aromatase and mTOR, has not been explored in LAM tissue. We first examined immunoreactivity for sex steroid receptors (estrogen receptor [ER] α, ERβ, progesterone receptor, androgen receptor), sex steroid-synthesizing enzymes (aromatase, steroid sulfatase, 17β-hydroxysteroid dehydrogenase 1, 5α-reductases), apoptotic suppression factor (Bcl-2), and factors involved in the mTOR signaling pathway in 30 pulmonary LAM tissues. Immunoreactivity for ERα, ERβ, progesterone receptor, aromatase, and Bcl-2 was significantly more abundant in epithelioid cells, whereas the status of androgen receptor, 5α-reductases, and phospho-mTOR signaling was not different in epithelioid and spindle-shaped LAM cells. We further examined the correlation among H scores of these markers using hierarchical clustering analysis. The results indicated that LAM tumors can be further classified into "aromatase" and "mTOR" groups on the basis of the patterns of immunoreactivity, and the 2 types could benefit from different modes of therapy.
authors: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Department of Anesthesiology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Koko
authors: K
authors: Adachi
authors: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Yasuhiro
authors: Y
authors: Miki
authors: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Ryoko
authors: R
authors: Saito
authors: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Shuko
authors: S
authors: Hata
authors: Department of Anesthesiology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Masanori
authors: M
authors: Yamauchi
authors: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto 606-8507, Japan.
authors: Yoshiki
authors: Y
authors: Mikami
authors: Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
authors: Yoshinori
authors: Y
authors: Okada
authors: Department of Respiratory Medicine, Juntendo University Faculty of Medicine, Tokyo 113-8431, Japan.
authors: Kuniaki
authors: K
authors: Seyama
authors: Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
authors: Takashi
authors: T
authors: Kondo
authors: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: hsasano@patholo2.med.tohoku.ac.jp.
authors: Hironobu
authors: H
authors: Sasano
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000328:Adult; D001141:Aromatase / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D018192:Lymphangioleiomyomatosis / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D011944:Receptors, Androgen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000502:physiology*; D043266:Steryl-Sulfatase / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055815:Young Adult
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D050794:STAT1 Transcription Factor; D015067:17-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D043266:Steryl-Sulfatase
keywords: Aromatase; Bcl-2; Estrogen; Pulmonary lymphangioleiomyomatosis; mTOR