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Methylation-induced downregulation of TFPI-2 causes TMPRSS4 overexpression and contributes to oncogenesis in a subset of non-small-cell lung carcinoma.

Hamamoto J, Soejima K, Naoki K, Yasuda H, Hayashi Y, Yoda S, Nakayama S, Satomi R, Terai H, Ikemura S, Sato T, Arai D, Ishioka K, Ohgino K, Betsuyaku T - Cancer Sci. (2014)

Bottom Line: Interestingly, we found that TMPRSS4 expression was associated with tissue factor pathway inhibitor 2 (TFPI-2) expression in these clinical samples.Knockdown of TMPRSS4 reduced the proliferation rate in several lung cancer cell lines.We found a novel molecular mechanism that TFPI-2 negatively regulates cell growth by inhibiting transcription of TMPRSS4.

View Article: PubMed Central - PubMed

Affiliation: Department of Pulmonary Medicine, School of Medicine, Keio University, Tokyo, Japan.

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Growth inhibition in lung cancer cells by 5-aza-2′-deoxycytidine or trichostatin A (TSA). (a–d) Cell growth was measured by a proliferation assay from day 0 to day 4 for 5-aza-2′-deoxycytidine or day 5 for TSA and calculated as fold change from day 0. NCI-H358 (a, d), NCI-H520 (b, e) and NCI-H1975 (c, f) cells were seeded at 5000 cells/well for NCI-H358 and 1000 cells/well for others, and treatment with 5 or 10 μM 5-aza-2′-deoxycytidine (a–c) or 0.05 or 0.1 μM TSA (d–f) was given on day 1. *P < 0.05 compared to 0 (DMSO alone). Data are representative of three independent experiments.
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fig06: Growth inhibition in lung cancer cells by 5-aza-2′-deoxycytidine or trichostatin A (TSA). (a–d) Cell growth was measured by a proliferation assay from day 0 to day 4 for 5-aza-2′-deoxycytidine or day 5 for TSA and calculated as fold change from day 0. NCI-H358 (a, d), NCI-H520 (b, e) and NCI-H1975 (c, f) cells were seeded at 5000 cells/well for NCI-H358 and 1000 cells/well for others, and treatment with 5 or 10 μM 5-aza-2′-deoxycytidine (a–c) or 0.05 or 0.1 μM TSA (d–f) was given on day 1. *P < 0.05 compared to 0 (DMSO alone). Data are representative of three independent experiments.

Mentions: The TFPI-2 gene was methylated in several lung cancer cell lines, including NCI-H358, NCI-H520, and NCI-H1975 (Fig.5b). When these cells were treated with the methylation inhibitor 5-aza-2′-deoxycytidine (5 μM) or the histone deacetylase inhibitor TSA (0.5 μM), the methylation level of TFPI-2 decreased and the mRNA expression level of TFPI-2 dramatically increased (Fig.5c,d). Conversely, these inhibitors reduced TMPRSS4 expression (Fig.5e). Finally, these agents inhibited the growth of these cell lines (Fig.6).


Methylation-induced downregulation of TFPI-2 causes TMPRSS4 overexpression and contributes to oncogenesis in a subset of non-small-cell lung carcinoma.

Hamamoto J, Soejima K, Naoki K, Yasuda H, Hayashi Y, Yoda S, Nakayama S, Satomi R, Terai H, Ikemura S, Sato T, Arai D, Ishioka K, Ohgino K, Betsuyaku T - Cancer Sci. (2014)

Growth inhibition in lung cancer cells by 5-aza-2′-deoxycytidine or trichostatin A (TSA). (a–d) Cell growth was measured by a proliferation assay from day 0 to day 4 for 5-aza-2′-deoxycytidine or day 5 for TSA and calculated as fold change from day 0. NCI-H358 (a, d), NCI-H520 (b, e) and NCI-H1975 (c, f) cells were seeded at 5000 cells/well for NCI-H358 and 1000 cells/well for others, and treatment with 5 or 10 μM 5-aza-2′-deoxycytidine (a–c) or 0.05 or 0.1 μM TSA (d–f) was given on day 1. *P < 0.05 compared to 0 (DMSO alone). Data are representative of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317784&req=5

fig06: Growth inhibition in lung cancer cells by 5-aza-2′-deoxycytidine or trichostatin A (TSA). (a–d) Cell growth was measured by a proliferation assay from day 0 to day 4 for 5-aza-2′-deoxycytidine or day 5 for TSA and calculated as fold change from day 0. NCI-H358 (a, d), NCI-H520 (b, e) and NCI-H1975 (c, f) cells were seeded at 5000 cells/well for NCI-H358 and 1000 cells/well for others, and treatment with 5 or 10 μM 5-aza-2′-deoxycytidine (a–c) or 0.05 or 0.1 μM TSA (d–f) was given on day 1. *P < 0.05 compared to 0 (DMSO alone). Data are representative of three independent experiments.
Mentions: The TFPI-2 gene was methylated in several lung cancer cell lines, including NCI-H358, NCI-H520, and NCI-H1975 (Fig.5b). When these cells were treated with the methylation inhibitor 5-aza-2′-deoxycytidine (5 μM) or the histone deacetylase inhibitor TSA (0.5 μM), the methylation level of TFPI-2 decreased and the mRNA expression level of TFPI-2 dramatically increased (Fig.5c,d). Conversely, these inhibitors reduced TMPRSS4 expression (Fig.5e). Finally, these agents inhibited the growth of these cell lines (Fig.6).

Bottom Line: Interestingly, we found that TMPRSS4 expression was associated with tissue factor pathway inhibitor 2 (TFPI-2) expression in these clinical samples.Knockdown of TMPRSS4 reduced the proliferation rate in several lung cancer cell lines.We found a novel molecular mechanism that TFPI-2 negatively regulates cell growth by inhibiting transcription of TMPRSS4.

View Article: PubMed Central - PubMed

Affiliation: Department of Pulmonary Medicine, School of Medicine, Keio University, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus