Activation of MAPK signaling pathway is essential for Id-1 induced serum independent prostate cancer cell growth.
The helix-loop-helix protein Id-1 has been suggested to play a positive role in cell proliferation and tumorigenesis of many types of human cancers. However, little is known about the molecular mechanism involved in the function of Id-1. In this study, using four stable Id-1 transfectant clones, we investigated the involvement of MAPK signaling pathway in the Id-1 induced serum independent prostate cancer cell growth. Our results demonstrated that both transient and stable ectopic Id-1 expression in prostate cancer LNCaP cells led to activation of the Raf/MEK1/2 signaling pathway. In addition, inhibition of MEK1/2 phosphorylation by one of its inhibitors, PD098059, resulted in the decreased cell cycle S phase fraction and cell growth rate, suggesting that activation of MAPK signaling pathway is essential for Id-1 induced prostate cancer cell proliferation. Furthermore, treatment with antisense oligonucleotide complementary to Id-1 mRNA in PC-3 and DU145 cells resulted in a decreased Id-1 expression which was accompanied by decreased Egr-1 protein. Our results suggest for the first time that the function of Id-1 is associated with MAPK signaling pathway activation and indicate a possible novel mechanism in which Id-1 regulates prostate cancer cell growth and tumorigenesis.
Ling
Ming-Tat
MT
Cancer Biology Laboratory, Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
Wang
Xianghong
X
Ouyang
Xue-Song
XS
Lee
Terence K W
TK
Fan
Tian-Yong
TY
Xu
Kexin
K
Tsao
Sai-Wah
SW
Wong
Y C
YC
D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D017874:Immediate-Early Proteins; D051798:Inhibitor of Differentiation Protein 1; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C497453:ID1 protein, human; D017874:Immediate-Early Proteins; D051798:Inhibitor of Differentiation Protein 1; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors