This Article Full Text Full Text (PDF) All Versions of this Article: 1078-0432.CCR-07-1950v1 14/14/4417    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Niikawa, H. Articles by Sasano, H. Search for Related Content PubMed PubMed Citation Articles by Niikawa, H. Articles by Sasano, H.

Intratumoral Estrogens and Estrogen Receptors in Human Non–Small Cell Lung Carcinoma

Authors' Affiliations: ¹ Department of Pathology, Tohoku University School of Medicine; ² Departments of Pathology and ³ Molecular Medical Technology, Tohoku University School of Health Sciences; ⁴ Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; ⁵ Department of Thoracic Surgery, Ishinomaki Red Cross Hospital, Ishinomaki, Japan; ⁶ Teizo Medical Co. Ltd., Kawasaki, Japan; and ⁷ Novartis Institutes for BioMedical Research Basel, Oncology Research, Basel, Switzerland

Requests for reprints: Takashi Suzuki, Department of Pathology, Tohoku University School of Health Sciences, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Phone: 81-22-717-8050; Fax: 81-22-717-8051; E-mail: t-suzuki{at}patholo2.med.tohoku.ac.jp.

Purpose: The possible involvement of gender-dependent factors has been suggested in human non-small cell lung carcinomas (NSCLC), but their precise roles remain largely unclear. Therefore, we examined intratumoral estradiol concentrations in NSCLC to examine local actions of estrogens in NSCLC.

Experimental Design: Fifty-nine frozen specimens of NSCLC were available for liquid chromatography/electrospray tandem mass spectrometry to study intratumoral estradiol concentrations. In addition, A549 NSCLC cells stably expressing estrogen receptor (ER) (A549 + ER) or ERβ (A549 + ERβ) were used in vitro studies.

Results: Forty-three (73%) of 59 NSCLC showed higher concentration of estradiol in carcinoma tissues than the corresponding nonneoplastic lung tissues from the same patient, and intratumoral estradiol concentrations were significantly (P = 0.0002 and 2.2-fold) higher than the corresponding nonneoplastic lungs. The intratumoral concentration of estradiol was positively correlated with aromatase expression, tumor size, and Ki-67 status in ER- or ERβ-positive cases. In in vitro studies, estradiol significantly increased cell proliferation of A549 + ER or A549 + ERβ, which was significantly suppressed by selective ER modulators, tamoxifen or raloxifene. Both A549 + ER and A549 + ERβ cells expressed aromatase. The cell proliferation level in these cells was significantly increased under treatment with testosterone, and it was inhibited by addition of the aromatase inhibitor letrozole.

Conclusions: These results suggest that estradiol is locally produced in NSCLC mainly by aromatase and plays an important role in the growth of ER- or ERβ-positive NSCLC. Therefore, use of selective ER modulators and/or aromatase inhibitors may be clinically effective in NSCLC that are positive for both ER and aromatase.