Oncogenic Transformation by SEI-1 Is Associated with Chromosomal Instability

Abstract

Amplification of SEI-1, a cell cycle regulatory gene at 19q13.1, is commonly detected in ovarian cancer, suggesting a role in the pathogenesis of ovarian cancer. In the present study, the oncogenic potential of SEI-1 was shown by anchorageindependent growth and tumor formation in nude mice with SEI-1-transfected NIH 3T3 mouse fibroblast cells. Silencing of SEI-1 gene expression by small interfering RNAs in ovarian cancer cell line SKOV3 could inhibit cell growth as well as colony formation on soft agar. Chromosomal alterations including the formation of double minutes were observed in tumor cells derived from SEI-1-transformed NIH 3T3 cells. Micronulei formation, which is an indicator of nuclear abnormality and genomic instability, was markedly increased in SEI-1 -transfected cells. These data suggest that the oncogenic role of SEI-1 might be mediated at least in part via an effect on genomic instability. Furthermore, overexpression of SEI-1 was associated with higher tumor grades and late Fesddration Internationale des Gynaecologistes et Obstetristes (FIGO) stages in ovarian carcinomas. These data strongly suggest that SEI-1 plays an important role in the development and progression of ovarian cancer. (Cancer Res 2005; 65(15): 6504-8)

Characterization of a Novel Mechanism of Genomic Instability Involving the SEI1/SET/NM23H1 Pathway in Esophageal Cancers

“…For example, overexpression of Aurora-A, a centrosome-associated kinase, can induce genetic instability as characterized by centrosome amplification, chromosome tetraploidization, and premature sister chromatid segregation (29). In our previous study, we found that the oncogenic role of SEI1 was associated with its effect on chromosomal instability (14). However, the molecular mechanism of how SEI1 induces genomic instability remains unclear.…”

“…Expression of SEI1 in SEI1-on cells was knocked down by RNA interference using small interfering RNAs (siRNA) against SEI1 as previously described (14). Double-stranded siRNAs were transiently transfected into SEI1-on cells using Lipofectamine 2000 (Invitrogen) according to the manufacturer's instruction.…”

“…A recent study found that p34 SEI1 could inhibit apoptosis through the stabilization of the X-linked inhibitor of apoptosis protein (13). Our previous study indicated that the oncogenic function of SEI1 was associated with chromosome instability (14). Ectopic expression of SEI1 could markedly increase the frequencies of chromosomal alteration and micronulei formation.…”

DNA copy number gains in head and neck squamous cell carcinoma

“…In all, novel sequences were detected. Interestingly, some of these regions (1q41, 7p22, 8p11.23, 8q13.1, 8q22.3, 10q21.3, 10q24.32, 19q13.1, 20p11.23) have been described as amplified sequences in other human malignancies (Bruch et al, 1998;Curtis et al, 1998;Du Plessis et al, 1999;Larramendy et al, 2000;Pimkhaokham et al, 2000;Tang et al, 2002;Dai et al, 2003;Lukasova et al, 2004;Rao et al, 2004). The RLGS data does not allow us to discriminate between DNA copy number gains that have integrated at the location of the original sequence or extra DNA localized in extrachromosomal double minutes.…”

p34SEI-1 Inhibits Apoptosis through the Stabilization of the X-Linked Inhibitor of Apoptosis Protein: p34SEI-1 as a Novel Target for Anti–Breast Cancer Strategies

“…Previous studies have shown that the SEI-1 gene is highly expressed in carcinomas from pancreatic (2), lung (3), and ovarian tissues (4), suggesting that p34 SEI-1 functions as an oncoprotein. Interestingly, recent studies have shown that p34 is capable of oncogenic transformation of mouse fibroblasts (5). However, it is not clear whether p34…”