Androgen receptor and androgen-dependent gene expression in lung.
The androgen receptor (AR) mediates the effects of male sex steroids. There are major sex differences in lung development and pathologies, including lung cancer. In this report, we show that Ar is mainly expressed in type II pneumocytes and the bronchial epithelium of murine lung and that androgen treatment increases AR protein levels in lung cells. Androgen administration altered significantly murine lung gene expression profiles; for example, by up-regulating transcripts involved in oxygen transport and down-regulating those in DNA repair and DNA recombination. Androgen exposure also affected the gene expression profile in a human lung adenocarcinoma-derived cell line, A549, by up- or down-regulating significantly some 200 transcripts, including down-regulation of genes involved in cell respiration. Dexamethasone treatment of A549 cells augmented expression of transcript sets that overlapped in part with those up-regulated by androgen in these cells. Moreover, a human lung cancer tissue array revealed that different lung cancer types are all AR-positive. Our results indicate that adult lung is an AR target tissue and suggest that AR plays a role in lung cancer biology.
Mikkonen
Laura
L
Biomedicum Helsinki, Institute of Biomedicine (Physiology), University of Helsinki, FI-00014 Helsinki, Finland.
Pihlajamaa
Päivi
P
Sahu
Biswajyoti
B
Zhang
Fu-Ping
FP
Jänne
Olli A
OA
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000728:Androgens; D005938:Glucocorticoids; D006454:Hemoglobins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D013739:Testosterone; D003907:Dexamethasone