Unknown

Dataset Information

0

Intratumoral localization and activity of 17?-hydroxysteroid dehydrogenase type 1 in non-small cell lung cancer: a potent prognostic factor.


ABSTRACT:

Background

Estrogens were recently demonstrated to be synthesized in non-small cell lung carcinomas (NSCLCs) via aromatase activity and aromatase inhibitor (AI) did suppressed estrogen receptor (ER) positive NSCLC growth. However, other enzymes involved in intratumoral production and metabolism of estrogens, i.e. 17?-hydroxysteroid dehydrogenases (i.e. 17?HSD1 and 17?HSD2) and others have not been studied. Therefore, in this study, we examined the clinical/ biological significance of 17?-hydroxysteroid dehydrogenases in NSCLCs.

Methodology

Archival materials obtained from 103 NSCLC patients were immunohistochemically evaluated using anti-17?HSD1 and anti-17?HSD2 antibodies. The findings of immunohistochemistry were then correlated with intratumoral estrone (E1) and estradiol (E2) concentration, clinicopathological factors and overall survival of the patients. We further employed NSCLC cell lines, A549 and LK87 to study the functional significance of 17?HSD1, in vitro.

Results

A higher 17?HSD1 immunoreactivity tended to be positively associated with aromatase (p=0.057) and tumor stage (p=0.055) whereas a higher 17?HSD2 immunoreactivity was positively associated with a squamous cell and adenosquamous cell carcinomas subtypes (p=0.031), tumor stage (p=0.004), T factor of TNM classification (p=0.010), maximum tumor diameter (p=0.002) and tended to be associated with N factor of TMN classification (p=0.065). A higher 17?HSD1 immunoreactivity was also significantly associated with lower intratumoral E1 concentration (p=0.040) and a higher intratumoral E2/E1 concentration ratio (p=0.028). On the other hand a higher 17?HSD2 immunoreactivity was significantly associated with higher intratumoral E1 concentration (p=0.035). Results of multivariate regression analysis demonstrated an increased 17?HSD1 immunoreactivity in tumor cells as an independent negative prognostic factor (HR= 2.83, p=0.007). E1 treatment in 17?HSD1 positive NSCLC cells, A549 and LK87, resulted in E2 production (p<0.0001) and enhanced cell proliferation, which was abrogated effectively by 17?HSD1 siRNA knockdown (p<0.0001). In addition, aromatase inhibitor treatment resulted in 17?HSD1 up regulation in both A549 and LK87 cells.

Conclusion

Results of our present study suggest that 17?HSD1 may be considered an important prognostic factor in NSCLC patients and targeting 17?HSD1 activity may further improve the clinical response in estrogen responsive NSCLC patients.

SUBMITTER: Verma MK 

PROVIDER: S-EPMC3724709 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Intratumoral localization and activity of 17β-hydroxysteroid dehydrogenase type 1 in non-small cell lung cancer: a potent prognostic factor.

Verma Mohit K MK   Miki Yasuhiro Y   Abe Keiko K   Suzuki Takashi T   Niikawa Hiromichi H   Suzuki Satoshi S   Kondo Takashi T   Sasano Hironobu H  

Journal of translational medicine 20130709


<h4>Background</h4>Estrogens were recently demonstrated to be synthesized in non-small cell lung carcinomas (NSCLCs) via aromatase activity and aromatase inhibitor (AI) did suppressed estrogen receptor (ER) positive NSCLC growth. However, other enzymes involved in intratumoral production and metabolism of estrogens, i.e. 17β-hydroxysteroid dehydrogenases (i.e. 17βHSD1 and 17βHSD2) and others have not been studied. Therefore, in this study, we examined the clinical/ biological significance of 17β  ...[more]

Similar Datasets

| S-EPMC7170045 | biostudies-literature
| S-EPMC10449848 | biostudies-literature
| S-EPMC5355379 | biostudies-literature
| S-EPMC7835108 | biostudies-literature
| S-EPMC8667298 | biostudies-literature
| S-EPMC8627256 | biostudies-literature
| S-EPMC3510433 | biostudies-literature
| S-EPMC3170876 | biostudies-literature
| S-EPMC5342153 | biostudies-literature
| S-EPMC3153478 | biostudies-literature