Abstract
Previous data from this group demonstrate that the murine lung metabolizes estrogen. Production of the putative carcinogen 4-hydroxyestrogen (4-OHE) is elevated within the lungs of female vs. male mice and accelerated by tobacco smoke. The goal of this study was to determine if the human lung metabolizes estrogen and evaluate the impact of tumor formation, smoke, sex and race/ethnicity on metabolism. Urine and lung tissue (normal, tumor) were obtained from 49 non-small cell lung cancer patients. Healthy postmenopausal Caucasian (n = 19) and Chinese (n = 20) American women (never-smokers) donated urine. Quantitative RT-PCR analyses indicate that multiple estrogen synthesis and metabolism genes are expressed in human bronchoalveolar cells. Estrogen and its metabolites were measured in lung tissue and urine using liquid chromatography/tandem mass spectrometry. Wilcoxon rank tests were used for statistical comparisons. E1, E2, E3 and estrogen metabolites 2-OHE1, 2-OHE2, 4-OHE1, 4-OHE2, 2-OME1 and 2-OME2 were detected at higher levels in tumor vs. adjacent normal tissue and in women vs. men (P < 0.05). The proportion of 4-OHEs was higher in tumors than in normal lung tissue (P < 0.05), and elevated in normal tissue from currentvs. never-smoking women (P = 0.006); similar trends were observed in urine. The proportion of 4-OHEs in the urine of postmenopausal Chinese American women was 1.8- fold higher than that of Caucasian women (P = 0.015). These data indicate that estrogen metabolites are present in the human lung. A shift towards 4-hydroxylation during lung tumorigenesis may contribute to the risk conferred by smoking, sex or race/ethnicity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 106778-106789 |
| Number of pages | 12 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 63 |
| DOIs | |
| State | Published - Jan 1 2017 |
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Keywords
- 4-hydroxy estrogen
- Estrogen metabolism
- Never-smoking Chinese women
- Non-small cell lung cancer
- Tobacco smoke
Cite this
Estrogen metabolism in the human lung : Impact of tumorigenesis, smoke, sex and race/ethnicity. / Peng, Jing; Meireles, Sibele I.; Xu, Xia; Smith, William E.; Slifker, Michael J.; Riel, Stacy L.; Zhai, Shumenghui; Zhang, Guo; Ma, Xiang; Kurzer, Mindy S.; Ma, Grace X.; Clapper, Margie L.
In: Oncotarget, Vol. 8, No. 63, 01.01.2017, p. 106778-106789.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Estrogen metabolism in the human lung
T2 - Impact of tumorigenesis, smoke, sex and race/ethnicity
AU - Peng, Jing
AU - Meireles, Sibele I.
AU - Xu, Xia
AU - Smith, William E.
AU - Slifker, Michael J.
AU - Riel, Stacy L.
AU - Zhai, Shumenghui
AU - Zhang, Guo
AU - Ma, Xiang
AU - Kurzer, Mindy S.
AU - Ma, Grace X.
AU - Clapper, Margie L.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Previous data from this group demonstrate that the murine lung metabolizes estrogen. Production of the putative carcinogen 4-hydroxyestrogen (4-OHE) is elevated within the lungs of female vs. male mice and accelerated by tobacco smoke. The goal of this study was to determine if the human lung metabolizes estrogen and evaluate the impact of tumor formation, smoke, sex and race/ethnicity on metabolism. Urine and lung tissue (normal, tumor) were obtained from 49 non-small cell lung cancer patients. Healthy postmenopausal Caucasian (n = 19) and Chinese (n = 20) American women (never-smokers) donated urine. Quantitative RT-PCR analyses indicate that multiple estrogen synthesis and metabolism genes are expressed in human bronchoalveolar cells. Estrogen and its metabolites were measured in lung tissue and urine using liquid chromatography/tandem mass spectrometry. Wilcoxon rank tests were used for statistical comparisons. E1, E2, E3 and estrogen metabolites 2-OHE1, 2-OHE2, 4-OHE1, 4-OHE2, 2-OME1 and 2-OME2 were detected at higher levels in tumor vs. adjacent normal tissue and in women vs. men (P < 0.05). The proportion of 4-OHEs was higher in tumors than in normal lung tissue (P < 0.05), and elevated in normal tissue from currentvs. never-smoking women (P = 0.006); similar trends were observed in urine. The proportion of 4-OHEs in the urine of postmenopausal Chinese American women was 1.8- fold higher than that of Caucasian women (P = 0.015). These data indicate that estrogen metabolites are present in the human lung. A shift towards 4-hydroxylation during lung tumorigenesis may contribute to the risk conferred by smoking, sex or race/ethnicity.
AB - Previous data from this group demonstrate that the murine lung metabolizes estrogen. Production of the putative carcinogen 4-hydroxyestrogen (4-OHE) is elevated within the lungs of female vs. male mice and accelerated by tobacco smoke. The goal of this study was to determine if the human lung metabolizes estrogen and evaluate the impact of tumor formation, smoke, sex and race/ethnicity on metabolism. Urine and lung tissue (normal, tumor) were obtained from 49 non-small cell lung cancer patients. Healthy postmenopausal Caucasian (n = 19) and Chinese (n = 20) American women (never-smokers) donated urine. Quantitative RT-PCR analyses indicate that multiple estrogen synthesis and metabolism genes are expressed in human bronchoalveolar cells. Estrogen and its metabolites were measured in lung tissue and urine using liquid chromatography/tandem mass spectrometry. Wilcoxon rank tests were used for statistical comparisons. E1, E2, E3 and estrogen metabolites 2-OHE1, 2-OHE2, 4-OHE1, 4-OHE2, 2-OME1 and 2-OME2 were detected at higher levels in tumor vs. adjacent normal tissue and in women vs. men (P < 0.05). The proportion of 4-OHEs was higher in tumors than in normal lung tissue (P < 0.05), and elevated in normal tissue from currentvs. never-smoking women (P = 0.006); similar trends were observed in urine. The proportion of 4-OHEs in the urine of postmenopausal Chinese American women was 1.8- fold higher than that of Caucasian women (P = 0.015). These data indicate that estrogen metabolites are present in the human lung. A shift towards 4-hydroxylation during lung tumorigenesis may contribute to the risk conferred by smoking, sex or race/ethnicity.
KW - 4-hydroxy estrogen
KW - Estrogen metabolism
KW - Never-smoking Chinese women
KW - Non-small cell lung cancer
KW - Tobacco smoke
UR - http://www.scopus.com/inward/record.url?scp=85036618329&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85036618329&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.22269
DO - 10.18632/oncotarget.22269
M3 - Article
C2 - 29290988
AN - SCOPUS:85036618329
VL - 8
SP - 106778
EP - 106789
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 63
ER -