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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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Related in: MedlinePlus

Immunohistochemical TMPRSS4/TFPI-2 staining of non-small-cell lung carcinoma (NSCLC) specimens. (a) Representative images of TMPRSS4 and TFPI-2 staining. (b) Scatter diagram represents the relationship between the expression score of TMPRSS4 (y-axis) and TMPRSS4mRNA expression level (x-axis) in six NSCLC specimens. The expression score was calculated by multiplying the proportion (%) with the intensity score of immunohistochemical analysis. The mRNA expression level was calculated as log10 ratios to average expression level of non-malignant region according to cDNA microarray data. (c) Same scatter diagram for TFPI-2 as for TMPRSS4 in (b). (d) Scatter diagram represents the relationship between the expression score of TMPRSS4 (y-axis) and TFPI-2 (x-axis) in six NSCLC specimens.
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fig02: Immunohistochemical TMPRSS4/TFPI-2 staining of non-small-cell lung carcinoma (NSCLC) specimens. (a) Representative images of TMPRSS4 and TFPI-2 staining. (b) Scatter diagram represents the relationship between the expression score of TMPRSS4 (y-axis) and TMPRSS4mRNA expression level (x-axis) in six NSCLC specimens. The expression score was calculated by multiplying the proportion (%) with the intensity score of immunohistochemical analysis. The mRNA expression level was calculated as log10 ratios to average expression level of non-malignant region according to cDNA microarray data. (c) Same scatter diagram for TFPI-2 as for TMPRSS4 in (b). (d) Scatter diagram represents the relationship between the expression score of TMPRSS4 (y-axis) and TFPI-2 (x-axis) in six NSCLC specimens.

Mentions: The expression of TMPRSS4 and TFPI-2 was analyzed by immunohistochemistry in six cases (Fig.2). These cases included three ACs and three SCCs. TMPRSS4 was expressed mainly in the cell membrane and also in the cytoplasm of cancer cells, and TFPI-2 was expressed in the cytoplasm of cancer cells (Fig.2a). TMPRSS4 was not expressed in stromal cells, whereas TFPI-2 was expressed not only in cancer cells but also in elastic fiber and smooth muscle cells. Although the sample size was small and might not be representative of all cases, protein and mRNA expressions showed weak correlation for both genes (rs = 0.348 for TMPRSS4; rs = 0.395 for TFPI-2) (Fig.2b,c), and the protein expressions of these genes seemed to be negatively correlated (rs = −0.524) (Fig.2d).


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)

Immunohistochemical TMPRSS4/TFPI-2 staining of non-small-cell lung carcinoma (NSCLC) specimens. (a) Representative images of TMPRSS4 and TFPI-2 staining. (b) Scatter diagram represents the relationship between the expression score of TMPRSS4 (y-axis) and TMPRSS4mRNA expression level (x-axis) in six NSCLC specimens. The expression score was calculated by multiplying the proportion (%) with the intensity score of immunohistochemical analysis. The mRNA expression level was calculated as log10 ratios to average expression level of non-malignant region according to cDNA microarray data. (c) Same scatter diagram for TFPI-2 as for TMPRSS4 in (b). (d) Scatter diagram represents the relationship between the expression score of TMPRSS4 (y-axis) and TFPI-2 (x-axis) in six NSCLC specimens.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Immunohistochemical TMPRSS4/TFPI-2 staining of non-small-cell lung carcinoma (NSCLC) specimens. (a) Representative images of TMPRSS4 and TFPI-2 staining. (b) Scatter diagram represents the relationship between the expression score of TMPRSS4 (y-axis) and TMPRSS4mRNA expression level (x-axis) in six NSCLC specimens. The expression score was calculated by multiplying the proportion (%) with the intensity score of immunohistochemical analysis. The mRNA expression level was calculated as log10 ratios to average expression level of non-malignant region according to cDNA microarray data. (c) Same scatter diagram for TFPI-2 as for TMPRSS4 in (b). (d) Scatter diagram represents the relationship between the expression score of TMPRSS4 (y-axis) and TFPI-2 (x-axis) in six NSCLC specimens.
Mentions: The expression of TMPRSS4 and TFPI-2 was analyzed by immunohistochemistry in six cases (Fig.2). These cases included three ACs and three SCCs. TMPRSS4 was expressed mainly in the cell membrane and also in the cytoplasm of cancer cells, and TFPI-2 was expressed in the cytoplasm of cancer cells (Fig.2a). TMPRSS4 was not expressed in stromal cells, whereas TFPI-2 was expressed not only in cancer cells but also in elastic fiber and smooth muscle cells. Although the sample size was small and might not be representative of all cases, protein and mRNA expressions showed weak correlation for both genes (rs = 0.348 for TMPRSS4; rs = 0.395 for TFPI-2) (Fig.2b,c), and the protein expressions of these genes seemed to be negatively correlated (rs = −0.524) (Fig.2d).

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