Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53.

Mercer, W E; Shields, M T; Amin, Mira; Sauvé, Gordon J.; Appella, Ettore; Romano, Joseph; Ullrich, Stephen J.

doi:10.1073/pnas.87.16.6166

Cited by 440 publications

(260 citation statements)

References 38 publications

Supporting

Mentioning

243

Contrasting

Unclassified

Order By: Relevance

“…Mutations in p53 (20), Rb (21), p16 (22), MMAC1 (23) and DCC (24) genes have been correlated with the initiation and progression of human gliomas. Amplification and/or activation of oncogenes, such as the genes for the epidermal growth factor receptor (25), transforming growth factor-␣ (26), MET (8), N-myc (5), c-myc (6), and gli (27) are thought to contribute to glioma formation by elevated expression of proteins that participate in mitogenic signalling pathways.…”

Section: Discussionmentioning

confidence: 99%

Missense Mutation of the MET Gene Detected in Human Glioma

et al. 2000

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Missense Mutation of the MET Gene Detected in Human Glioma

et al. 2000

View full text Add to dashboard Cite

“…14,15 Studies on glioblastomas have shown that overexpression of wt-p53 suppress cell growth, and induces apoptotic cell death in vitro and in vivo. [16][17][18][19] These findings have rendered p53 a potentially helpful target for gene therapy of brain tumors. However, one of the main obstacles of gene therapy is the lack of efficient vectors for gene transduction to express high levels of the protein of interest in the large majority of the tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Increase of BCNU sensitivity by wt-p53 gene therapy in glioblastoma lines depends on the administration schedule

Biroccio¹,

Bufalo²,

Ricca³

et al. 1999

Gene Ther

View full text Add to dashboard Cite

In this article, we investigated the effect induced by the ify the cell cycle profile in respect of Ad-p53 infected cells. reintroduction of wild-type p53 (wt-p53) protein on BCNU In contrast, BCNU→Ad-p53 sequence provoked G2-M sensitivity in the ADF glioblastoma line. Using a wt-p53 rearrest similar to that observed after treatment with BCNU combinant adenovirus (Ad-p53), we demonstrated that alone, but prevented the later recovery of the cells through exogenous wt-p53 expression was able to increase the the cell cycle, by driving the cells to apoptotic death. These sensitivity to BCNU in ADF cells. Interestingly, this effect results demonstrate that the administration sequence is was more evident when Ad-p53 infection was performed important to increase drug sensitivity. To generalize the after BCNU treatment compared with the opposite phenomenon observed on ADF line, the antiproliferative sequence. To understand the biological basis of these difeffect of the two different schedules was analyzed on other ferent behaviors, we analyzed the cell cycle of the differglioblastoma lines (A172, CRS-A2, U373MG) with different ently treated cells. We found that Ad-p53 infection induced BCNU sensitivity and p53 status. The data obtained a persistent accumulation of cells in the G0/G1 phase confirm that the wt-p53 gene transfer enhances BCNU while, as expected, BCNU induced a block in the G2-M sensitivity in glioblastoma cells depending on the phase. Ad-p53→BCNU sequence did not significantly modadministration sequence.

show abstract

“…After incubation at 37°C for 24 hr, cells were evaluated for the presence of ␤-galactosidaseexpressing cells (blue). The X-gal staining solution contained the following reagents: 1.3 mM MgCl 2 , 15 mM NaCl, 44 mM Tris, pH 7.4, 3 mM K 4 Fe(CN) 6 -3H 2 O, 3 mM K 3 Fe(CN) 6 and 0.5 mg/ml of X-gal.…”

Section: Ad-lacz Infection and X-gal Stainingmentioning

confidence: 99%

“…For studying the role of p53 in these mechanisms, wild-type (WT) p53 function was restored in various glioblastoma cell lines by several gene transfer methods, including stable transfection of p53 constructs inducible by dexamethasone 6 or tetracycline, 7 an exogenous murine p53 Val 135 temperature-sensitive (ts) mutant, 8 p53 expression from retroviruses 9 and adenoviruses. 10 Expression of p53 in glioblastoma cells from stably transfected clones or retrovirally transduced genes induced growth arrest or senescence, whereas expression from adenoviruses induced apoptosis.…”

mentioning

confidence: 99%

Restoration of endogenous wild-type p53 activity in a glioblastoma cell line with intrinsic temperature-sensitive p53 induces growth arrest but not apoptosis

Ikeda¹,

Tada²,

Ishii³

et al. 2001

Int. J. Cancer

View full text Add to dashboard Cite

p53 protein is a transcription factor involved in multiple tumor-suppressor activities including cell cycle control and apoptosis. TP53 gene is frequently mutated in glioblastoma, suggesting the importance of inactivation of this gene product in gliomagenesis. Restoration of p53 function in glioblastoma cell lines deficient for p53 has shown that p53 induces growth arrest or apoptosis depending on the cell line and vector used to transduce wild-type TP53 alleles. Considering that astrocytes grow and express p53, it is not clear whether these results reflect physiologic responses or the result of p53 overexpression in combination with cellular responses to viral vector infection. Here, we reassessed this issue using a glioblastoma cell line (LN382) that expresses an endogenous temperature-sensitive mutant p53. This cell line expresses TP53 alleles (100% as determined by a p53 transcriptional assay in yeast) mutated at codon 197 GTG (Val) > CTG (Leu). We found that the p53 protein in these cells acted as an inactive mutant at 37°C and as a functional wild-type p53 below 34°C as demonstrated by several lines of evidence, including (i) restoration of transactivating ability in yeast, (ii) induction of p53-modulated genes such as CDKN1 p21 and transforming growth factor-␣, (iii) disappearance of accumulated p53 protein in the nucleus and (iv) decrease in steady state p53 protein levels. This temperature switch allowed p53 levels, which were close to physiological levels to dramatically reduce LN382 cell proliferation by inducing a G 1 /S cell cycle block, but not to induce apoptosis. The lack of apoptosis was considered to be a result of the low level p53 expression, because increasing wild-type p53 levels by adenoviral-mediated gene transfer caused apoptosis in these cells. The LN382 cell line will be extremely useful for investigations into the roles of p53 in cellular responses to a variety of stimuli or damages.

show abstract

Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53.

Cited by 440 publications

References 38 publications

Missense Mutation of the MET Gene Detected in Human Glioma

Missense Mutation of the MET Gene Detected in Human Glioma

Increase of BCNU sensitivity by wt-p53 gene therapy in glioblastoma lines depends on the administration schedule

Restoration of endogenous wild-type p53 activity in a glioblastoma cell line with intrinsic temperature-sensitive p53 induces growth arrest but not apoptosis

Contact Info

Product

Resources

About