Dickkopf-1 induced apoptosis in human placental choriocarcinoma is independent of canonical Wnt signaling.
Placental choriocarcinoma, a reproductive system carcinoma in women, has about 0.81% occurrence frequency in China, which leads to over 90% lethality due to indistinct pathogenesis and the absence of efficient therapeutic treatment. In the present study, using immunostaining and reverse transcription PCR, we reported that Dickkopf-1 (Dkk-1) is prominently expressed in human cytotrophoblast (CTB) cell, but absent in the human placental choriocarcinoma cell line JAR and JEG3, implicating an unknown correlation between Dkk-1 and carcinogenesis of placental choriocarcinoma. Further, through exogenous introduction of Dkk-1, we found repressed proliferation in JAR and JEG3, induced apoptosis in JAR, and discovered significant tumor suppression effects of Dkk-1 in placental choriocarcinoma. Moreover we found that this function of Dkk-1 is achieved through c-Jun N-terminal kinase (JNK), whereas the canonical Wnt pathway may not have a great role. This discovery is not symphonic to previous functional understanding of Dkk-1, a canonical Wnt signaling antagonist. Together, our data indicate the possible correlation between Dkk-1 and human placental choriocarcinoma and suggest potential applications of Dkk-1 in treatment of human placental choriocarcinomas.
Peng
Sha
S
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China.
Miao
Chenglin
C
Li
Jing
J
Fan
Xiujun
X
Cao
Yujing
Y
Duan
Enkui
E
D017209:Apoptosis / Q000187:drug effects*; D002822:Choriocarcinoma / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects*; D014594:Uterine Neoplasms / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*
C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins