Estrogen inhibits cell proliferation through in situ production in human thymoma

Hironori Ishibashi, Takashi Suzuki, Satoshi Suzuki, Takuya Moriya, Chika Kaneko, Taisuke Nakata, Makoto Sunamori, Masashi Handa, Takashi Kondo, Hironobu Sasano

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12 Citations (Scopus)


Purpose: We showed previously estrogen receptor (ER) α as an independent prognostic marker in human thymoma. Estrogen sulfotransferase (EST), steroid sulfatase (STS), 17β-hydroxysteroid dehydrogenase (17β-HSD), and aromatase are considered to play important roles in hormone metabolism of estrogen-dependent tumors. Experimental Design: We examined estrogen production using primary cultures of human thymoma epithelial cells (TEC), intratumoral estradiol (E2) concentrations, and status of these enzymes above using immunohistochemistry or semiquantitative reverse transcription-PCR. We then correlated these findings with clinicopathologic variables and/or clinical outcome in 132 patients. Results: E2 inhibited cell proliferation via ERα in TEC, which synthesized estrone and E2. Intratumoral E2 concentrations were inversely correlated with EST, positively correlated with STS or 17β-HSD type 1, and significantly higher in lower-grade or early-stage thymoma. EST status was positively correlated with tumor size, clinical stage, histologic differentiation, and Ki-67 labeling index and significantly associated with adverse clinical outcome and turned out to be a potent independent prognostic factor. STS and/or 17β-HSD type 1 status was inversely correlated with Ki-67 labeling index and associated with lower histologic grade or early clinical stages. Conclusions: E2 inhibits proliferation of TEC through ERα, which suggests that E2 may be effective in treatment of thymoma, especially inoperable tumor, possibly through suppressing its cell proliferation activity. EST status is a potent prognostic factor in thymoma through inactivating estrogens. In situ estrogen synthesis through intracrine mechanism therefore may play important roles in tumorigenesis and/or development of thymoma through regulation of cell proliferation in an intracrine manner.

Original languageEnglish
Pages (from-to)6495-6504
Number of pages10
JournalClinical Cancer Research
Issue number18
Publication statusPublished - 2005 Sept 15


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