Suppression of transformed phenotype and tumorigenicity after transfer of chromosome 4 into U251 human glioma cells

Pershouse, Mark A.; Ligon, Azra H.; Pereira‐Smith, Olivia M.; Killary, Ann M.; Yung, W. K. Alfred; Steck, Peter A.

doi:10.1002/(sici)1098-2264(199711)20:3<260::aid-gcc6>3.3.co;2-j

Cited by 10 publications

(12 citation statements)

References 17 publications

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“…In some cases, these losses appear to be mutually exclusive suggesting that there may well be a number of different genes on chromosome 10 that are important for gliomagenesis, which might also account for the observation that the most frequent event is the loss of the whole chromosome. Transfer of an intact copy of chromosome 10 from normal cells into GBM cell lines results in suppression of malignancy, which further supports the suggestion that critical glioma genes are located on this chromosome (Pershouse et al, 1993). The fact that the whole chromosome is lost, however, makes it difficult to incriminate any particular gene.…”

Section: Introductionsupporting

confidence: 70%

Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene

2003

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The leucine-rich, glioma-inactivated (LGI1) gene, located in 10q24, was originally identified because it was interrupted and inactivated by a reciprocal chromosome translocation in the T98G glioma cell line. Loss of LGI1 expression in high-grade brain tumors is correlated with the frequent loss of chromosome 10 during progression of gliomas. To investigate whether this gene can suppress the malignant phenotype in glioma cells, we introduced the LGI1 gene into cells that do (U87) and do not (T98G and A172) express LGI1 endogenously. A172 and T98G cells showed a significant reduction in cell proliferation potential as a result of re-expression of LGI1, whereas U87 cells did not. Using BD matrigel matrix chamber assays we were also able to show that the migration ability of the reconstituted A172 and T98G cells was also reduced considerably. Finally, these reconstituted T98G and A172 cells showed a significant reduction in the ability to form colonies in soft agar compared with the parental cells. This analysis clearly demonstrates that re-expression of the LGI1 gene in glioma cells that were null for its activity can greatly reduce their malignant potential. These observations provide the opportunity to investigate the role of LGI1 in gliomagenesis and, since LGI1 is predicted to be a membrane-bound protein, potentially provides the opportunity to develop novel treatment strategies for malignant gliomas.

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Section: Introductionsupporting

confidence: 70%

Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene

2003

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“…Recent cytogenetic studies revealed that loss on 10q is also frequent in SCLCs (Ried et al, 1994;Petersen et al, 1997). Functional analysis by fusion of normal chromosome 10 into glioblastoma cells that had lost a complete copy of chromosome 10 resulted in signi®cantly decreased colony formation in soft agarose and complete suppression of tumor formation in vivo (Pershouse et al, 1993). These data further support the idea that a tumor-suppressor gene (or genes) is present in chromosome 10.…”

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confidence: 52%

Identification of two distinct tumor-suppressor loci on the long arm of chromosome 10 in small cell lung cancer

Kim

Kemp

et al. 1998

Oncogene

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Recent cytogenetic studies indicated that loss of the long arm of chromosome 10 is a frequent event in small cell lung cancer (SCLC) and that a common region of the deletion is at 10q24-qter, which suggests the presence of a tumor-suppressor gene there. To map precise tumorsuppressor loci on the chromosome arm for further positional cloning e orts, we tested 46 primary SCLCs using microsatellite analysis. By analysing 11 highly polymorphic microsatellite markers located in 10q23-q26, we found that at least 78% (36/46) of the tumors exhibited loss of heterozygosity (LOH) at 10q with at least two distinct minimally deleted regions. LOH at one region (10q24) was found in at least 74% (32/43) of informative cases with a minimally deleted region between D10S198 and D10S192 (about 2 cM); LOH at another region (10q24-q25) was observed in at least 66% (29/44) of informative tumors with a minimally deleted region between D10S221 and D10S587 (about 11 cM). LOH at both regions or across both regions was observed in at least 52% (24/46) of the tumors tested. However, no mutations or homozygous deletions were found in the coding region of MXI1, a candidate tumor suppressor gene at 10q24-q25, in a panel of SCLC cell lines. Our data demonstrate that at least two tumorsuppressor loci exist on 10q and that they may play an important role in SCLC tumorigenesis.

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“…Further evidence for the signi®cance of these putative tumor suppressor genes on chromosome 10 in the pathogenesis of gliomas was provided by microcellmediated chromosomal transfer. The glioma cell line U251-MG exhibited a suppression of growth in soft agar and of tumor formation in nude mice upon introduction of an intact chromosome 10 (Pershouse et al, 1993). Similar experiments also point to a functional link between chromosome 10 genes in malignant gliomas and angiogenesis.…”

Section: Introductionmentioning

confidence: 53%

PTEN mutations in gliomas and glioneuronal tumors

et al. 1998

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Cytogenetic and loss of heterozygosity studies have suggested the presence of at least one tumor suppressor gene on chromosome 10 involved in the formation of high grade gliomas. Recently, the PTEN gene, also termed MMAC1 or TEP1, on chromosomal band 10q23 has been identi®ed. Initial studies revealed mutations of PTEN in limited series of glioma cell lines and glioblastomas. In order to systematically evaluate the involvement of PTEN in gliomas, we have analysed the entire PTEN coding sequence by SSCP and direct sequencing in a series of 331 gliomas and glioneuronal tumors. PTEN mutations were detected in 20/142 glioblastomas, 1/7 giant cell glioblastomas, 1/2 gliosarcomas, 1/30 pilocytic astrocytomas and 2/22 oligodendrogliomas. No PTEN mutations were detected in 52 astrocytomas, 37 oligoastrocytomas, three subependymal giant cell astrocytomas, four pleomorphic xanthoastrocytomas, 15 ependymomas, 16 gangliogliomas and one dysembryoplastic neuroepithelial tumor. In addition, all tumors were examined for the presence of homozygous deletions of the PTEN gene; these were detected in 7 glioblastomas that did not have PTEN mutations. Therefore, PTEN mutations occur in approximately 20% of glioblastomas but are rare in lower grade gliomas. These ®ndings con®rm that PTEN is one of the chromosome 10 tumor suppressor genes involved in the development of glioblastomas.

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Suppression of transformed phenotype and tumorigenicity after transfer of chromosome 4 into U251 human glioma cells

Cited by 10 publications

References 17 publications

Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene

Suppression of the cell proliferation and invasion phenotypes in glioma cells by the LGI1 gene

Identification of two distinct tumor-suppressor loci on the long arm of chromosome 10 in small cell lung cancer

PTEN mutations in gliomas and glioneuronal tumors

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