原创力文档5-alpha-reductase type i (srd5a1) is up-regulated in non-small cell lung cancer but does not impact proliferation, cell cycle distribution or apoptosisα还原i型(srd5a1)上调在非小细胞肺癌,但并不影响扩散,细胞周期分布和细胞凋亡.pdfVIP
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5-alpha-reductase type i (srd5a1) is up-regulated in non-small cell lung cancer but does not impact proliferation, cell cycle distribution or apoptosisα还原i型(srd5a1)上调在非小细胞肺癌,但并不影响扩散,细胞周期分布和细胞凋亡
Kapp et al. Cancer Cell International 2012, 12:1
/content/12/1/1
PRIMARY RESEARCH Open Access
5-alpha-reductase type I (SRD5A1) is up-regulated
in non-small cell lung cancer but does not
impact proliferation, cell cycle distribution or
apoptosis
1,2 1 2 2 1*
Friedrich G Kapp , Anette Sommer , Thomas Kiefer , Gottfried Dölken and Bernard Haendler
Abstract
Background: Non-small cell lung cancer (NSCLC) is one of the most frequent malignancies and has a high
mortality rate due to late detection and lack of efficient treatments. Identifying novel drug targets for this
indication may open the way for new treatment strategies. Comparison of gene expression profiles of NSCLC and
normal adjacent tissue (NAT) allowed to determine that 5-alpha-reductase type I (SRD5A1) was up-regulated in
NSCLC compared to NAT. This raised the question whether SRD5A1 was involved in sustained proliferation and
survival of NSCLC.
Methods: siRNA-mediated silencing of SRD5A1 was performed in A549 and NCI-H460 lung cancer cell lines in
order to determine the impact on proliferation, on distribution during the different phases of the cell cycle, and on
apoptosis/necrosis. In addition, lung cancer cell lines were treated with 4-azasteroids, which specifically inhibit
SRD5A1 activity, and the effects on proliferation were measured. Statistical analyses using ANOVA and post-hoc
Tamhane-T2-test were performed. In the case of non-parametric data, the Kruskal-Wallis test and the post-hoc
Mann-Whitney-U-test were used.
Results: The knock-down of SRDA51 expression was very efficient with the SRD5A1 transcripts being reduced to
10% of control levels. Knock-down efficiency was furthermore confirmed at the protein level. However, n
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