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Polypeptide N-acetylgalactosaminyltransferase 2 regulates cellular metastasis-associated behavior in gastric cancer.

Hua D, Shen L, Xu L, Jiang Z, Zhou Y, Yue A, Zou S, Cheng Z, Wu S - Int. J. Mol. Med. (2012)

Bottom Line: We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells.However, it did not exhibit any apparent correlation with MMP-14 expression levels.Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1.

View Article: PubMed Central - PubMed

Affiliation: Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China.

ABSTRACT
Aberrant glycosylation of cell surface glycoprotein due to specific alterations of glycosyltransferase activity is usually associated with invasion and metastasis of cancer, particularly of gastric carcinomas. Polypeptide N-acetylgalactosaminyltransferase 2 (ppGalNAc-T2), which catalyzes initiation of mucin-type O-glycosylation, is also involved in tumor migration and invasion. However, a comprehensive understanding of how ppGalNAc-T2 correlates with the metastasic potential of human gastric cancer is not currently available. In the present study, ppGalNAc-T2 was detected in a variety of human poorly differentiated tumor cells, and expression appeared to be higher in SGC7901 gastric cancer cells. In addition, we investigated the potential effects of ppGalNAc-T2 on growth and metastasis-associated behavior in SGC7901 cells after stable transfection with ppGalNAc-T2 sense and antisense vectors. We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells. Therefore, we attempted to clarify the mechanisms underlying the anti-metastatic activities of ppGalNAc-T2. Further investigation indicated that overexpression of ppGalNAc-T2 is involved in the inhibition of matrix metalloproteinase (MMP)-2 expression at both the protein and mRNA levels, which may be associated with ppGalNAc-T2 suppressing the expression of transforming growth factor (TGF)-β1. However, it did not exhibit any apparent correlation with MMP-14 expression levels. Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1. These results indicate that ppGalNAc‑T2 may be used as a novel therapeutic target for human gastric cancer treatment.

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Upregulation of ppGalNAc-T2 inhibits human gastric cancer cell proliferation invitro. SGC7901 cells and their transfectants were cultured in 96-well platesat 5x103/well for 24, 48, 72, 96 and 120 h. Cell growth was assessed by MTTassay.
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f4-ijmm-30-06-1267: Upregulation of ppGalNAc-T2 inhibits human gastric cancer cell proliferation invitro. SGC7901 cells and their transfectants were cultured in 96-well platesat 5x103/well for 24, 48, 72, 96 and 120 h. Cell growth was assessed by MTTassay.

Mentions: To examine whether modulation of ppGalNAc-T2 expression affects the tumorigenicproperties of the gastric cancer cells, we measured the abilities of invitro cell proliferation by MTT assay. The untreated SGC7901, control, as wellas the SGC7901-T2s and SGC7901-T2as cells were grown in culture for 5 days. The ability ofcell proliferation in the SGC7901-T2s cells was decreased compared with the control oruntreated cells but increased in the SGC7901-T2as cells (P>0.05) (Fig. 4). Treatment of SGC7901 cells withppGalNAc-T2 sense vectors was associated with a time-dependent inhibition of cell growth,whereas no significant inhibitory effect was observed in the untreated and control cells.These results indicate that multi-step molecular events are necessary for the function ofppGalNAc-T2 to switch the SGC7901 cells from a proliferative state to an inhibited stateof cell growth.


Polypeptide N-acetylgalactosaminyltransferase 2 regulates cellular metastasis-associated behavior in gastric cancer.

Hua D, Shen L, Xu L, Jiang Z, Zhou Y, Yue A, Zou S, Cheng Z, Wu S - Int. J. Mol. Med. (2012)

Upregulation of ppGalNAc-T2 inhibits human gastric cancer cell proliferation invitro. SGC7901 cells and their transfectants were cultured in 96-well platesat 5x103/well for 24, 48, 72, 96 and 120 h. Cell growth was assessed by MTTassay.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042861&req=5

f4-ijmm-30-06-1267: Upregulation of ppGalNAc-T2 inhibits human gastric cancer cell proliferation invitro. SGC7901 cells and their transfectants were cultured in 96-well platesat 5x103/well for 24, 48, 72, 96 and 120 h. Cell growth was assessed by MTTassay.
Mentions: To examine whether modulation of ppGalNAc-T2 expression affects the tumorigenicproperties of the gastric cancer cells, we measured the abilities of invitro cell proliferation by MTT assay. The untreated SGC7901, control, as wellas the SGC7901-T2s and SGC7901-T2as cells were grown in culture for 5 days. The ability ofcell proliferation in the SGC7901-T2s cells was decreased compared with the control oruntreated cells but increased in the SGC7901-T2as cells (P>0.05) (Fig. 4). Treatment of SGC7901 cells withppGalNAc-T2 sense vectors was associated with a time-dependent inhibition of cell growth,whereas no significant inhibitory effect was observed in the untreated and control cells.These results indicate that multi-step molecular events are necessary for the function ofppGalNAc-T2 to switch the SGC7901 cells from a proliferative state to an inhibited stateof cell growth.

Bottom Line: We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells.However, it did not exhibit any apparent correlation with MMP-14 expression levels.Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1.

View Article: PubMed Central - PubMed

Affiliation: Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China.

ABSTRACT
Aberrant glycosylation of cell surface glycoprotein due to specific alterations of glycosyltransferase activity is usually associated with invasion and metastasis of cancer, particularly of gastric carcinomas. Polypeptide N-acetylgalactosaminyltransferase 2 (ppGalNAc-T2), which catalyzes initiation of mucin-type O-glycosylation, is also involved in tumor migration and invasion. However, a comprehensive understanding of how ppGalNAc-T2 correlates with the metastasic potential of human gastric cancer is not currently available. In the present study, ppGalNAc-T2 was detected in a variety of human poorly differentiated tumor cells, and expression appeared to be higher in SGC7901 gastric cancer cells. In addition, we investigated the potential effects of ppGalNAc-T2 on growth and metastasis-associated behavior in SGC7901 cells after stable transfection with ppGalNAc-T2 sense and antisense vectors. We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells. Therefore, we attempted to clarify the mechanisms underlying the anti-metastatic activities of ppGalNAc-T2. Further investigation indicated that overexpression of ppGalNAc-T2 is involved in the inhibition of matrix metalloproteinase (MMP)-2 expression at both the protein and mRNA levels, which may be associated with ppGalNAc-T2 suppressing the expression of transforming growth factor (TGF)-β1. However, it did not exhibit any apparent correlation with MMP-14 expression levels. Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1. These results indicate that ppGalNAc‑T2 may be used as a novel therapeutic target for human gastric cancer treatment.

Show MeSH
Related in: MedlinePlus