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Báo cáo y học: "Hedgehog overexpression leads to the formation of prostate cancer stem cells with metastatic property irrespective of androgen receptor expression in the mouse model"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Hedgehog overexpression leads to the formation of prostate cancer stem cells with metastatic property irrespective of androgen receptor expression in the mouse model | Chang et al. Journal of Biomedical Science 2011 18 6 http www.jbiomedsci.eom content 18 1 6 tì NSC The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Hedgehog overexpression leads to the formation of prostate cancer stem cells with metastatic property irrespective of androgen receptor expression in the mouse model 11 21 1 1 z i1 3 4 Han-Hsin Chang Bo-Yie Chen Chia-Yung Wu Zih-Jay Tsao Ying-Yu Chen Chin-Pao Chang Chi-Rei Yang David Pei-Cheng Lin2 5 6 Abstract Background Hedgehog signalling has been implicated in prostate tumorigenesis in human subjects and mouse models but its effects on transforming normal basal stem cells toward malignant cancer stem cells remain poorly understood. Methods We produced pCX-shh-IG mice that overexpress Hedgehog protein persistently in adult prostates allowing for elucidation of the mechanism during prostate cancer initiation and progression. Various markers were used to characterize and confirm the transformation of normal prostate basal stem cells into malignant cancer stem cells under the influence of Hedgehog overexpression. Results The pCX-shh-IG mice developed prostatic intraepithelial neoplasia PIN that led to invasive and metastatic prostate cancers within 90 days. The prostate cancer was initiated through activation of P63 basal stem cells along with simultaneous activation of Hedgehog signalling members suggesting that P63 Patch1 and P63 Smo cells may serve as cancer-initiating cells and progress into malignant prostate cancer stem cells PCSCs . In the hyperplastic lesions and tumors the progeny of PCSCs differentiated into cells of basal-intermediate and intermediate-luminal characteristics whereas rare ChgA neuroendocrine differentiation was seen. Furthermore in the metastatic loci within lymph nodes kidneys and lungs the P63 PCSCs formed prostate-like glandular structures characteristic of the primitive structures .