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Increased expressio...
Increased expression of insulin-like growth factor I receptor in malignant cells expressing aberrant p53 : Functional impact
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- Girnita, L. (författare)
- Karolinska Institutet
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- Girnita, A. (författare)
- Karolinska Institutet
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- Brodin, B. (författare)
- Karolinska Institutet
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Xie, Y. T. (författare)
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- Nilsson, G. (författare)
- Karolinska Institutet
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Dricu, A. (författare)
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- Lundeberg, Joakim (författare)
- KTH,Bioteknologi
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- Wejde, J. (författare)
- Karolinska Institutet
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- Bartolazzi, A. (författare)
- Karolinska Institutet
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- Wiman, K. G. (författare)
- Karolinska Institutet
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- Larsson, O. (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2000
- 2000
- Engelska.
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 60:18, s. 5278-5283
- Relaterad länk:
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- We investigated the functional impact of p53 on insulin-like growth factor I receptor (IGF-IR) expression in malignant cells. Using the BL-41tsp53-2 cell line, a transfectant carrying temperature-sensitive (ts) p53 and endogenous mutant p53 (codon 248), we demonstrated a drastic down-regulation of plasma membrane-bound IGF-IRs on induction of wild-type p53, However, a similar response was obtained by treatment of BL-41tsp53-2 cells expressing mutant ts p53 with a p53 antisense oligonucleotide. Thus, even if the negative effect of wild-type p53 predominates under a competitive condition, these data indicate that mutant p53 may be important for up-regulation of IGF-IR, To further elucidate this issue, three melanoma cell lines (BE, SK-MEL-5, and SK-MEL-28) that over expressed p53 were investigated. The BE cell line has a hot spot mutation (codon 248) and expresses only codon 248-mutant p53, SK-MEL-28 has a point mutation at codon 145. SK-MEL-5 cells did not exhibit any p53 mutations, but the absence of p21(Waf1) expression suggested functionally aberrant p53. Our data suggest that interaction with Mdm-2 may underlie p53 inactivation in these cells, Using p53 antisense oligonucleotides, we demonstrated a substantial down-regulation of cell surface expression of IGF-IR proteins in all melanoma cell lines after 24 h, This was paralleled by decreased tyrosine phosphorylation of IGF-IR and growth arrest, and, subsequently, massive cell death was observed (this was also seen in BL-41tsp53-2 cells with mutant conformation of ts p53). Taken together, our results suggest that up-regulation of IGF-IR as a result of expression of aberrant p53 may be important for the growth and survival of malignant cells.
Nyckelord
- human-melanoma cells
- n-linked glycosylation
- mutant p53
- wild-type
- inhibition
- gene
- apoptosis
- mutation
- lines
- mechanisms
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
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Girnita, L.
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Girnita, A.
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Brodin, B.
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Xie, Y. T.
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Nilsson, G.
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Dricu, A.
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visa fler...
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Lundeberg, Joaki ...
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Wejde, J.
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Bartolazzi, A.
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Wiman, K. G.
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Larsson, O.
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visa färre...
- Artiklar i publikationen
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Cancer Research
- Av lärosätet
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Kungliga Tekniska Högskolan
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Karolinska Institutet