Sil overexpression in lung cancer characterizes tumors with increased mitotic activity.
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.
Erez
Ayelet
A
Department of Pediatric Hemato-Oncology, The Chaim Sheba Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel.
Perelman
Marina
M
Hewitt
Stephen M
SM
Cojacaru
Gadi
G
Goldberg
Iris
I
Shahar
Iris
I
Yaron
Pnina
P
Muler
Inna
I
Campaner
Stefano
S
Amariglio
Ninette
N
Rechavi
Gideon
G
Kirsch
Ilan R
IR
Krupsky
Meir
M
Kaminski
Naftali
N
Izraeli
Shai
S
D000230:Adenocarcinoma / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D016193:G1 Phase; D017781:Genes, Immediate-Early; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D018386:Kinetochores / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D008938:Mitosis; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C071236:STIL protein, human