Sil overexpression in lung cancer characterizes tumors with increased mitotic activity

被引:51
作者
Erez, A
Perelman, M
Hewitt, SM
Cojacaru, G
Goldberg, I
Shahar, I
Yaron, P
Muler, I
Campaner, S
Amariglio, N
Rechavi, G
Kirsch, IR
Krupsky, M
Kaminski, N
Izraeli, S
机构
[1] Chaim Sheba Med Ctr, Chaim Sheba Canc Res Ctr, Dept Pediat Hematooncol, IL-52621 Tel Hashomer, Israel
[2] Chaim Sheba Med Ctr, Chaim Sheba Canc Res Ctr, Dept Pathol, IL-52621 Tel Hashomer, Israel
[3] NIH, Ctr Adv Technol, Bethesda, MD 20892 USA
[4] Chaim Sheba Med Ctr, Chaim Sheba Canc Res Ctr, Dept Funct Gen, IL-52621 Tel Hashomer, Israel
[5] Compugen LTD, Tel Aviv, Israel
[6] Chaim Sheba Med Ctr, Chaim Sheba Canc Res Ctr, Dept Pulm Med, IL-52621 Tel Hashomer, Israel
[7] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel
[8] NCI, NIH, Bethesda, MD 20892 USA
[9] Univ Pittsburgh, Med Ctr, Dorothy P & Richard P Simmons Ctr, Pittsburgh, PA 15261 USA
基金
以色列科学基金会;
关键词
Sil; mitosis; lung cancer; carcinogenesis;
D O I
10.1038/sj.onc.1207685
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Sil (SCL interrupting locus) was cloned from the most common chromosomal rearrangement in T-cell acute lymphoblastic leukemia. It is an immediate early gene whose expression is associated with cell proliferation. Sil protein levels are tightly regulated during the cell cycle, reaching peak levels in mitosis and disappearing on transition to G1. A recent study found Sil to be one of 17 genes whose overexpression in primary adenocarcinomas predicts metastatic spread. We hypothesized that Sil might have a role in carcinogenesis. To address this question, we utilized several approaches. Using a multi-tumor tissue array, we found that Sil protein expression was increased mostly in lung cancer, but also at lower levels, in a subset of other tumors. Microarray gene expression analysis and immunohistochemistry of lung cancer samples verified these observations. Sil gene expression in lung cancer correlated with the expression of several kinetochore check-point genes and with the histopathologic mitotic index. The se observations suggest that overexpression of the Sil gene characterizes tumors with increased mitotic activity.
引用
收藏
页码:5371 / 5377
页数:7
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