Intratumoral estrogens and estrogen receptors in human non-small cell lung carcinoma
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Niikawa, Hiromichi, Suzuki, Takashi, Miki, Yasuhiro, Suzuki, Satoshi, Nagasaki, Shuji, Akahira, Junichi, Honma, Seijiro, Evans, Dean Brent, Hayashi, Shin-Ichi, Kondo, Takashi and Sasano, Hironobu (2008) Intratumoral estrogens and estrogen receptors in human non-small cell lung carcinoma. Clinical Cancer Research : an official journal of the American Association for Cancer Research, 14 (14). pp. 4417-4426. ISSN 1078-0432
Abstract
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) alpha (A549 + ERalpha) or ERbeta (A549 + ERbeta) 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 ERalpha- or ERbeta-positive cases. In in vitro studies, estradiol significantly increased cell proliferation of A549 + ERalpha or A549 + ERbeta, which was significantly suppressed by selective ER modulators, tamoxifen or raloxifene. Both A549 + ERalpha and A549 + ERbeta 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 ERalpha- or ERbeta-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.
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| Additional Information: | Author can archive post-print (ie final draft post-refereeing); Authors final version may be deposited on institutional website/ repository if required by institution |
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| Date Deposited: | 22 Feb 2010 11:50 |
| Last Modified: | 22 Feb 2010 11:50 |
| URI: | https://oak.novartis.com/id/eprint/1671 |