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
N1 - Funding Information:
Grants-in-aid for Scientific Research on Priority Areas and Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Diseases from the Ministry of Education, Culture, Sports, Science, and Technology; Health and Labour Sciences Research Grant by the Ministry of Health, Labour and Welfare, Japan; Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation; New Energy and Industrial Technology Development Organization.
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.
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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 -