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 multitumor 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. These observations suggest that overexpression of the Sil gene characterizes tumors with increased mitotic activity.
Bibliographical noteFunding Information:
We thank Sergey Nemez for the statistical analysis. This study was supported by research grants from the Israel Science Foundation, the Israel Cancer Research foundation and from Tel-Aviv University Recanati foundation to S Izraeli. N Kaminski is the Dorothy P and Richard P Simmons chair of Interstitial Lung Diseases at the University of Pittsburgh Medical School. G Rechavi holds the Gregorio and Dora Shapiro Chair for Hematology Malignancies, Sackler School of Medicine, Tel-Aviv University. This work was preformed in partial fulfillment of the requirements for the PhD degree of Ayelet Erez, Sackler Faculty of Medicine, Tel-Aviv University.
- Lung cancer