Abstract
Although we have identified two putative targets, ATF3 and CENPF, for a frequently gained/amplified region around 1q32-41 in esophageal squamous cell carcinoma (ESCC), it is possible that other amplification targets remain to be identified. In this study, we tested whether SET and MYND domain-containing protein 2 (SMYD2), located between those two genes and encoding a lysine methyltransferase for histone H3K36 and p53K370 that regulates transcription and inhibits transactivation activity, respectively, acts as a cancer-promoting gene through activation/ overexpression in ESCC. Frequent overexpression of SMYD2 messenger RNA and protein was observed in KYSE150 cells with remarkable amplification at 1q32-41.1 and other ESCC cell lines (11/43 lines, 25.6%). Overexpression of SMYD2 protein was frequently detected in primary tumor samples of ESCC (117/153 cases, 76.5%) as well and significantly correlated with gender, venous invasion, the pT category in the tumor-lymph node-metastases classification and status of recurrence. Patients with SMYD2-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors, and SMYD2 positivity was independently associated with a worse outcome in the multivariate analysis. Knockdown of SMYD2 expression inhibited and ectopic overexpression of SMYD2 promoted the proliferation of ESCC cells in a TP53 mutation-independent but SMYD2 expression-dependent manner. These findings suggest that SMYD2 plays an important role in tumor cell proliferation through its activation/overexpression and highlight its usefulness as a prognosticator and potential therapeutic target in ESCC.
| Original language | English |
|---|---|
| Pages (from-to) | 1139-1146 |
| Number of pages | 8 |
| Journal | Carcinogenesis |
| Volume | 30 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2009 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
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Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma. / Komatsu, Shuhei; Imoto, Issei; Tsuda, Hitoshi; Kozaki, Ken Ich; Muramatsu, Tomoki; Shimada, Yutaka; Aiko, Satoshi; Yoshizumi, Yutaka; Ichikawa, Daisuke; Otsuji, Eigo; Inazawa, Johji.
In: Carcinogenesis, Vol. 30, No. 7, 2009, p. 1139-1146.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma
AU - Komatsu, Shuhei
AU - Imoto, Issei
AU - Tsuda, Hitoshi
AU - Kozaki, Ken Ich
AU - Muramatsu, Tomoki
AU - Shimada, Yutaka
AU - Aiko, Satoshi
AU - Yoshizumi, Yutaka
AU - Ichikawa, Daisuke
AU - Otsuji, Eigo
AU - Inazawa, Johji
PY - 2009
Y1 - 2009
N2 - Although we have identified two putative targets, ATF3 and CENPF, for a frequently gained/amplified region around 1q32-41 in esophageal squamous cell carcinoma (ESCC), it is possible that other amplification targets remain to be identified. In this study, we tested whether SET and MYND domain-containing protein 2 (SMYD2), located between those two genes and encoding a lysine methyltransferase for histone H3K36 and p53K370 that regulates transcription and inhibits transactivation activity, respectively, acts as a cancer-promoting gene through activation/ overexpression in ESCC. Frequent overexpression of SMYD2 messenger RNA and protein was observed in KYSE150 cells with remarkable amplification at 1q32-41.1 and other ESCC cell lines (11/43 lines, 25.6%). Overexpression of SMYD2 protein was frequently detected in primary tumor samples of ESCC (117/153 cases, 76.5%) as well and significantly correlated with gender, venous invasion, the pT category in the tumor-lymph node-metastases classification and status of recurrence. Patients with SMYD2-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors, and SMYD2 positivity was independently associated with a worse outcome in the multivariate analysis. Knockdown of SMYD2 expression inhibited and ectopic overexpression of SMYD2 promoted the proliferation of ESCC cells in a TP53 mutation-independent but SMYD2 expression-dependent manner. These findings suggest that SMYD2 plays an important role in tumor cell proliferation through its activation/overexpression and highlight its usefulness as a prognosticator and potential therapeutic target in ESCC.
AB - Although we have identified two putative targets, ATF3 and CENPF, for a frequently gained/amplified region around 1q32-41 in esophageal squamous cell carcinoma (ESCC), it is possible that other amplification targets remain to be identified. In this study, we tested whether SET and MYND domain-containing protein 2 (SMYD2), located between those two genes and encoding a lysine methyltransferase for histone H3K36 and p53K370 that regulates transcription and inhibits transactivation activity, respectively, acts as a cancer-promoting gene through activation/ overexpression in ESCC. Frequent overexpression of SMYD2 messenger RNA and protein was observed in KYSE150 cells with remarkable amplification at 1q32-41.1 and other ESCC cell lines (11/43 lines, 25.6%). Overexpression of SMYD2 protein was frequently detected in primary tumor samples of ESCC (117/153 cases, 76.5%) as well and significantly correlated with gender, venous invasion, the pT category in the tumor-lymph node-metastases classification and status of recurrence. Patients with SMYD2-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors, and SMYD2 positivity was independently associated with a worse outcome in the multivariate analysis. Knockdown of SMYD2 expression inhibited and ectopic overexpression of SMYD2 promoted the proliferation of ESCC cells in a TP53 mutation-independent but SMYD2 expression-dependent manner. These findings suggest that SMYD2 plays an important role in tumor cell proliferation through its activation/overexpression and highlight its usefulness as a prognosticator and potential therapeutic target in ESCC.
UR - http://www.scopus.com/inward/record.url?scp=67650102336&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67650102336&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgp116
DO - 10.1093/carcin/bgp116
M3 - Article
C2 - 19423649
AN - SCOPUS:67650102336
VL - 30
SP - 1139
EP - 1146
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 7
ER -