TY - JOUR
T1 - Gender-dependent expression of alpha and beta estrogen receptors in human nontumor and tumor lung tissue
AU - Fasco, Michael J.
AU - Hurteau, Gregory J.
AU - Spivack, Simon D.
N1 - Funding Information:
This work was supported in part by grant NIH/NIEHS K08 ES00298 (SS). The authors wish to thank Dr Ken Aldous, analytic chemistry, for nicotine, and cotinine assays; Dr Tim Zhimin Cao, clinical chemistry, estradiol immunoassay; the Molecular Genetics Core, Wadsworth center, for oligonucleotide synthesis and nucleotide sequencing; and Dr Brian Pentecost, Environmental Disease Prevention, for cloning the ERβ fragments.
PY - 2002/2/25
Y1 - 2002/2/25
N2 - Estrogen receptor (ER) expression in human lung has been understudied, particularly in light of its potential biological importance in the female lung cancer epidemic. Reverse transcription-polymerase chain reaction was used to probe mRNA expression of wild-type ERα and ERβ and their splice variants in human bronchogenic tumor and adjacent nontumor specimens. In tumor tissue from 13 women and 13 men, ERα was expressed in 85% of women versus 15% in men [P=0.001]. ERβ was expressed equally in tumors from women versus men [92% vs. 69%, P=ns]. Both ERα and β forms were expressed simultaneously in the lung tumors of 77% of women versus 15% of men [P=0.005]. Among adjacent nontumor lung specimens, 31% of the women expressed ERα mRNA versus 0% of men [P=0.101], and 39% of women expressed ERβ mRNA versus 31% of men [P=ns]; only one woman and no men expressed both ERα and β in nontumor tissue. Females expressed ERα [P=0.017], ERβ [P=0.013], and ERα+β [P=0.002] more frequently in tumor versus nontumor tissue, whereas in males expression of ERα, β and both α+β was not clearly different for tumor versus nontumor tissue. In specimens expressing ERα mRNA, the transcript lacking exon 7 (Δ7) was the major splice variant with varying contributions from the transcripts Δ4, Δ3+4, Δ5 and others unidentified. Alternative splicing of ERβ mRNA was observed, but not to as great an extent as for ERα mRNA. ERα promoter usage in tumors varied among individuals. When the ER receptors were co-expressed in tumors, ERα was quantitatively more abundant in the majority of cases than ERβ. Within this small group of 26 patients, no correlation was found between age, smoking history, plasma nicotine, cotinine, estradiol concentrations or histopathologic type with tumor or nontumor estrogen receptor status of any type. However, several positive correlations imply that: (1) ERα expression occurs more often in the lungs of women than men; (2) ERβ is expressed with approximately equal frequency in the lungs of both genders; and (3) tumors display a higher frequency of both receptor types than nontumors in women. We hypothesize that these putative gender-dependent differences in ERα and ERβ expression could contribute unique phenotypic characteristics to lung cancer development or progression in women.
AB - Estrogen receptor (ER) expression in human lung has been understudied, particularly in light of its potential biological importance in the female lung cancer epidemic. Reverse transcription-polymerase chain reaction was used to probe mRNA expression of wild-type ERα and ERβ and their splice variants in human bronchogenic tumor and adjacent nontumor specimens. In tumor tissue from 13 women and 13 men, ERα was expressed in 85% of women versus 15% in men [P=0.001]. ERβ was expressed equally in tumors from women versus men [92% vs. 69%, P=ns]. Both ERα and β forms were expressed simultaneously in the lung tumors of 77% of women versus 15% of men [P=0.005]. Among adjacent nontumor lung specimens, 31% of the women expressed ERα mRNA versus 0% of men [P=0.101], and 39% of women expressed ERβ mRNA versus 31% of men [P=ns]; only one woman and no men expressed both ERα and β in nontumor tissue. Females expressed ERα [P=0.017], ERβ [P=0.013], and ERα+β [P=0.002] more frequently in tumor versus nontumor tissue, whereas in males expression of ERα, β and both α+β was not clearly different for tumor versus nontumor tissue. In specimens expressing ERα mRNA, the transcript lacking exon 7 (Δ7) was the major splice variant with varying contributions from the transcripts Δ4, Δ3+4, Δ5 and others unidentified. Alternative splicing of ERβ mRNA was observed, but not to as great an extent as for ERα mRNA. ERα promoter usage in tumors varied among individuals. When the ER receptors were co-expressed in tumors, ERα was quantitatively more abundant in the majority of cases than ERβ. Within this small group of 26 patients, no correlation was found between age, smoking history, plasma nicotine, cotinine, estradiol concentrations or histopathologic type with tumor or nontumor estrogen receptor status of any type. However, several positive correlations imply that: (1) ERα expression occurs more often in the lungs of women than men; (2) ERβ is expressed with approximately equal frequency in the lungs of both genders; and (3) tumors display a higher frequency of both receptor types than nontumors in women. We hypothesize that these putative gender-dependent differences in ERα and ERβ expression could contribute unique phenotypic characteristics to lung cancer development or progression in women.
KW - Alternatively spliced estrogen receptor mRNAs
KW - Estrogen receptor mRNA analysis
KW - Estrogen receptor transcriptional regulation
KW - Gender
KW - Lung cancer
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U2 - 10.1016/S0303-7207(01)00750-X
DO - 10.1016/S0303-7207(01)00750-X
M3 - Article
C2 - 11911952
AN - SCOPUS:0037169815
SN - 0303-7207
VL - 188
SP - 125
EP - 140
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -
