TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival

Kenya Yoshida, Mitsuo Sato, Tetsunari Hase, Momen Elshazley, Ryo Yamashita, Noriyasu Usami, Tetsuo Taniguchi, Kohei Yokoi, Shigeo Nakamura, Masashi Kondo, Luc Girard, John D. Minna, Yoshinori Hasegawa

研究成果: Article

20 引用 (Scopus)

抄録

TIMELESS (TIM) is a mammalian homolog of a Drosophila circadian rhythm gene, but its circadian properties in mammals have yet to be determined. TIM appears to be essential for replication protection and genomic stability. Recently, the involvement of TIM in human malignancies has been reported; therefore, we investigated the role of TIM in lung cancer. Microarray expression analysis of lung cancer cell lines showed that TIM expression was elevated 3.7-fold (P < 0.001) in non-small cell lung cancer cell lines (n = 116) compared to normal lung controls (n = 59). In addition, small cell lung cancer cell lines (n = 29) expressed TIM at levels 2.2-fold (P < 0.001) higher than non-small cell lung cancer. Western blot analysis of 22 lung cancer cell lines revealed that all of them expressed TIM protein and that 20 cell lines (91%) expressed TIM protein at higher levels than a normal control line. Remarkably, immunohistochemistry of 30 surgically resected lung cancer specimens showed that all lung cancer specimens but no matched normal lung tissues were positive for TIM expression. Moreover, immunohistochemistry of surgically resected specimens from 88 consecutive patients showed that high TIM protein levels correlated with poor overall survival (P = 0.013). Mutation analysis for TIM in 23 lung cancer cell lines revealed no mutation. TIM knockdown suppressed proliferation and clonogenic growth, and induced apoptosis in H157 and H460 cells. Taken together, our findings suggest that TIM could be useful as a diagnostic and prognostic marker for lung cancer and targeting it would be of high therapeutic value for this disease.

元の言語English
ページ(範囲)171-177
ページ数7
ジャーナルCancer science
104
発行部数2
DOI
出版物ステータスPublished - 01-02-2013

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Lung Neoplasms
Survival
Cell Line
Non-Small Cell Lung Carcinoma
Immunohistochemistry
Lung
Mutation
Proteins
Genomic Instability
Small Cell Lung Carcinoma
Microarray Analysis
Circadian Rhythm
Drosophila
Mammals
Western Blotting
Apoptosis
Growth
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Yoshida, K., Sato, M., Hase, T., Elshazley, M., Yamashita, R., Usami, N., ... Hasegawa, Y. (2013). TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival. Cancer science, 104(2), 171-177. https://doi.org/10.1111/cas.12068
Yoshida, Kenya ; Sato, Mitsuo ; Hase, Tetsunari ; Elshazley, Momen ; Yamashita, Ryo ; Usami, Noriyasu ; Taniguchi, Tetsuo ; Yokoi, Kohei ; Nakamura, Shigeo ; Kondo, Masashi ; Girard, Luc ; Minna, John D. ; Hasegawa, Yoshinori. / TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival. :: Cancer science. 2013 ; 巻 104, 番号 2. pp. 171-177.
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abstract = "TIMELESS (TIM) is a mammalian homolog of a Drosophila circadian rhythm gene, but its circadian properties in mammals have yet to be determined. TIM appears to be essential for replication protection and genomic stability. Recently, the involvement of TIM in human malignancies has been reported; therefore, we investigated the role of TIM in lung cancer. Microarray expression analysis of lung cancer cell lines showed that TIM expression was elevated 3.7-fold (P < 0.001) in non-small cell lung cancer cell lines (n = 116) compared to normal lung controls (n = 59). In addition, small cell lung cancer cell lines (n = 29) expressed TIM at levels 2.2-fold (P < 0.001) higher than non-small cell lung cancer. Western blot analysis of 22 lung cancer cell lines revealed that all of them expressed TIM protein and that 20 cell lines (91{\%}) expressed TIM protein at higher levels than a normal control line. Remarkably, immunohistochemistry of 30 surgically resected lung cancer specimens showed that all lung cancer specimens but no matched normal lung tissues were positive for TIM expression. Moreover, immunohistochemistry of surgically resected specimens from 88 consecutive patients showed that high TIM protein levels correlated with poor overall survival (P = 0.013). Mutation analysis for TIM in 23 lung cancer cell lines revealed no mutation. TIM knockdown suppressed proliferation and clonogenic growth, and induced apoptosis in H157 and H460 cells. Taken together, our findings suggest that TIM could be useful as a diagnostic and prognostic marker for lung cancer and targeting it would be of high therapeutic value for this disease.",
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Yoshida, K, Sato, M, Hase, T, Elshazley, M, Yamashita, R, Usami, N, Taniguchi, T, Yokoi, K, Nakamura, S, Kondo, M, Girard, L, Minna, JD & Hasegawa, Y 2013, 'TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival', Cancer science, 巻. 104, 番号 2, pp. 171-177. https://doi.org/10.1111/cas.12068

TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival. / Yoshida, Kenya; Sato, Mitsuo; Hase, Tetsunari; Elshazley, Momen; Yamashita, Ryo; Usami, Noriyasu; Taniguchi, Tetsuo; Yokoi, Kohei; Nakamura, Shigeo; Kondo, Masashi; Girard, Luc; Minna, John D.; Hasegawa, Yoshinori.

:: Cancer science, 巻 104, 番号 2, 01.02.2013, p. 171-177.

研究成果: Article

TY - JOUR

T1 - TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival

AU - Yoshida, Kenya

AU - Sato, Mitsuo

AU - Hase, Tetsunari

AU - Elshazley, Momen

AU - Yamashita, Ryo

AU - Usami, Noriyasu

AU - Taniguchi, Tetsuo

AU - Yokoi, Kohei

AU - Nakamura, Shigeo

AU - Kondo, Masashi

AU - Girard, Luc

AU - Minna, John D.

AU - Hasegawa, Yoshinori

PY - 2013/2/1

Y1 - 2013/2/1

N2 - TIMELESS (TIM) is a mammalian homolog of a Drosophila circadian rhythm gene, but its circadian properties in mammals have yet to be determined. TIM appears to be essential for replication protection and genomic stability. Recently, the involvement of TIM in human malignancies has been reported; therefore, we investigated the role of TIM in lung cancer. Microarray expression analysis of lung cancer cell lines showed that TIM expression was elevated 3.7-fold (P < 0.001) in non-small cell lung cancer cell lines (n = 116) compared to normal lung controls (n = 59). In addition, small cell lung cancer cell lines (n = 29) expressed TIM at levels 2.2-fold (P < 0.001) higher than non-small cell lung cancer. Western blot analysis of 22 lung cancer cell lines revealed that all of them expressed TIM protein and that 20 cell lines (91%) expressed TIM protein at higher levels than a normal control line. Remarkably, immunohistochemistry of 30 surgically resected lung cancer specimens showed that all lung cancer specimens but no matched normal lung tissues were positive for TIM expression. Moreover, immunohistochemistry of surgically resected specimens from 88 consecutive patients showed that high TIM protein levels correlated with poor overall survival (P = 0.013). Mutation analysis for TIM in 23 lung cancer cell lines revealed no mutation. TIM knockdown suppressed proliferation and clonogenic growth, and induced apoptosis in H157 and H460 cells. Taken together, our findings suggest that TIM could be useful as a diagnostic and prognostic marker for lung cancer and targeting it would be of high therapeutic value for this disease.

AB - TIMELESS (TIM) is a mammalian homolog of a Drosophila circadian rhythm gene, but its circadian properties in mammals have yet to be determined. TIM appears to be essential for replication protection and genomic stability. Recently, the involvement of TIM in human malignancies has been reported; therefore, we investigated the role of TIM in lung cancer. Microarray expression analysis of lung cancer cell lines showed that TIM expression was elevated 3.7-fold (P < 0.001) in non-small cell lung cancer cell lines (n = 116) compared to normal lung controls (n = 59). In addition, small cell lung cancer cell lines (n = 29) expressed TIM at levels 2.2-fold (P < 0.001) higher than non-small cell lung cancer. Western blot analysis of 22 lung cancer cell lines revealed that all of them expressed TIM protein and that 20 cell lines (91%) expressed TIM protein at higher levels than a normal control line. Remarkably, immunohistochemistry of 30 surgically resected lung cancer specimens showed that all lung cancer specimens but no matched normal lung tissues were positive for TIM expression. Moreover, immunohistochemistry of surgically resected specimens from 88 consecutive patients showed that high TIM protein levels correlated with poor overall survival (P = 0.013). Mutation analysis for TIM in 23 lung cancer cell lines revealed no mutation. TIM knockdown suppressed proliferation and clonogenic growth, and induced apoptosis in H157 and H460 cells. Taken together, our findings suggest that TIM could be useful as a diagnostic and prognostic marker for lung cancer and targeting it would be of high therapeutic value for this disease.

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Yoshida K, Sato M, Hase T, Elshazley M, Yamashita R, Usami N その他. TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival. Cancer science. 2013 2 1;104(2):171-177. https://doi.org/10.1111/cas.12068