ADAM17 Regulates  Proliferation via the  EGFR-PI3K/Akt/p27 Pathway in Prostate Cancer Cells

WU Qi,FENG Tian,SUN Xi-Cai,LIN Ping,BIAN Shu-Ling,ZHAO Xu-Fei, LI Cong, YU Xiao-Guang

Chinese Journal of Biochemistry and Molecular Biology ›› 2010, Vol. 26 ›› Issue (8) : 749-755.

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Chinese Journal of Biochemistry and Molecular Biology ›› 2010, Vol. 26 ›› Issue (8) : 749-755.
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ADAM17 Regulates  Proliferation via the  EGFR-PI3K/Akt/p27 Pathway in Prostate Cancer Cells

  • WU Qi1),2) FENG Tian 1) , SUN Xi-Cai 1) , LIN Ping 1) , BIAN Shu-Ling 1) ,ZHAO Xu-Fei 1) ,  LI Cong 3) ,  YU Xiao-Guang 1)*
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Abstract

A Disintegrin and A Metalloproteinase 17 (ADAM17), a membrane-associated metalloproteinase, is involved in the proteolytic release of the ectodomain of diverse cell surface proteins with critical roles in the tumor proliferation and metastasis. We have previously demonstrated that ADAM17 is highly expressed in DU145 cells, compared with LNCap cells. In this study, we elucidate whether ADAM17 contributes to prostate cancer proliferation and mediates p27 mRNA expression, as well as the mechanism between them in vitro. The results of CCK-8 assay and cell quantification showed that ADAM17 expression correlated with prostate cancer cell proliferation. The results of Western blotting indicated that the expression of ADAM17 was down-regulated by GM6001 or ADAM17-siRNA in DU145, but it was up-regulated by PMA (an activator of ADAM17) in LNCap. Conversely,the result of RT-PCR indicated that p27 mRNA expression was up-regulated by GM6001 or ADAM17-siRNA in DU145, but it was down-regulated by PMA in LNCap. Furthermore, increased p27 mRNA expression level was associated with inhibition of the EGFR-PI3K/Akt signaling pathway, as confirmed by RT-PCR and Western blotting analysis. These results suggest that ADAM17 can mediate prostate cancer cell proliferation and P27 gene expression via EGFR-PI3K/Akt pathway.

Key words

prostate cancer / ADAM17 / pEGFR / pAkt / p27

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WU Qi,FENG Tian,SUN Xi-Cai,LIN Ping,BIAN Shu-Ling,ZHAO Xu-Fei, LI Cong, YU Xiao-Guang. ADAM17 Regulates  Proliferation via the  EGFR-PI3K/Akt/p27 Pathway in Prostate Cancer Cells[J]. Chinese Journal of Biochemistry and Molecular Biology, 2010, 26(8): 749-755

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Funding

Supported by National Natural Science Foundation of China (No.30772173) and National Natural Science Foundation of Heilongjiang Province, China (No. D2007-56)

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