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http://dx.doi.org/10.7314/APJCP.2012.13.5.2087

β3GnT8 Regulates Laryngeal Carcinoma Cell Proliferation Via Targeting MMPs/TIMPs and TGF-β1  

Hua, Dong (The Fourth Affiliated Hospital of Soochow University)
Qin, Fang (Department of Biochemistry and Mollecular Biology, School of Medicine, Soochow University)
Shen, Li (Department of Biochemistry and Mollecular Biology, School of Medicine, Soochow University)
Jiang, Zhi (Department of Biochemistry and Mollecular Biology, School of Medicine, Soochow University)
Zou, Shi-Tao (Department of Biochemistry and Mollecular Biology, School of Medicine, Soochow University)
Xu, Lan (Department of Biochemistry and Mollecular Biology, School of Medicine, Soochow University)
Cheng, Zhi-Hong (The Fourth Affiliated Hospital of Soochow University)
Wu, Shi-Liang (Department of Biochemistry and Mollecular Biology, School of Medicine, Soochow University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.5, 2012 , pp. 2087-2093 More about this Journal
Abstract
Previous evidence showed ${\beta}1$, 3-N-acetylglucosaminyltransferase 8 (${\beta}3GnT8$), which can extend polylactosamine on N-glycans, to be highly expressed in some cancer cell lines and tissues, indicating roles in tumorigenesis. However, so far, the function of ${\beta}3GnT8$ in laryngeal carcinoma has not been characterized. To test any contribution, Hep-2 cells were stably transfected with sense or interference vectors to establish cell lines that overexpressed or were deficient in ${\beta}3GnT8$. Here we showed that cell proliferation was increased in ${\beta}3GnT8$ overexpressed cells but decreased in ${\beta}3GnT8$ knockdown cells using MTT. Furthermore, we demonstrated that change in ${\beta}3GnT8$ expression had significant effects on tumor growth in nude mice.We further provided data suggesting that overexpression of ${\beta}3GnT8$ enhanced the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) at both the mRNA and protein levels, associated with shedding of tissue inhibitors of metalloproteinase TIMP-2. In addition, it caused increased production of transforming growth factor beta 1 (TGF-${\beta}1$), whereas ${\beta}3GnT8$ gene knockdown caused the reverse effect. The results may indicate a novel mechanism by which effects of ${\beta}3GnT8$ in regulating cellular proliferation are mediated, at least in partvia targeting MMPs/TIMPs and TGF-${\beta}1$ in laryngeal carcinoma Hep-2 cells. The finding may lay a foundation for further investigations into the ${\beta}3GnT8$ as a potential target for therapy of laryngeal carcinoma.
Keywords
${\beta}3GnT8$; proliferation; laryngeal carcinoma; MMP; TGF-${\beta}1$; therapy;
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