A mouse prostate cancer model induced by Hedgehog overexpression.
Hedgehog is a regulatory protein during embryonic development and its abnormal activation in adult tissues has been implicated in tumorigenesis within sites where epithelial-mesenchymal interactions take place. In the prostate, Hedgehog signaling activation was observed during advanced cancer progression and metastasis, but whether Hedgehog overexpression can initiate prostate tumorigenesis remains unknown. We introduced a Hedgehog-expressing vector by intra-prostate injection and electroporation to address the effects of Hedgehog overexpression. The manipulation caused lesions with characteristic prostatic intraepithelial neoplasia or even prostatic cancer (CaP) phenotypes within 30 days, with Hedgehog overexpression demonstrated by immunohistochemistry and Western blot detections. The tumorigenic phenotypes were confirmed by discontinuity of basal cell marker p63, mix-up of CK-8/CK-18 positive epithelial cells in the stoma as well as absence of alpha-SMA positive fibro-muscular sheath. Comparable Hedgehog overexpression was found in human CaP specimen. Thus, Hedgehog overexpression induced prostate tumorigenesis starting from the normal status. Furthermore, a mouse prostate cancer model induced by Hedgehog overexpression was established and may be used for testing novel therapeutical approaches targeting at Hedgehog signaling pathway.
Chen
Bo-Yie
BY
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
Lin
David Pei-Cheng
DP
Liu
Jer-Yuh
JY
Chang
Han
H
Huang
Po-Hsuan
PH
Chen
Yie-Ling
YL
Chang
Han-Hsin
HH
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008953:Models, Anatomic; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis*
D053823:Hedgehog Proteins; C509239:SHH protein, human; C465570:Shh protein, mouse; D015534:Trans-Activators