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Increased expressio...
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Girnita, L.Karolinska Institutet
(author)
Increased expression of insulin-like growth factor I receptor in malignant cells expressing aberrant p53 : Functional impact
- Article/chapterEnglish2000
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LIBRIS-ID:oai:DiVA.org:kth-20056
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-20056URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:1931520URI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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QC 20100525
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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.
Subject headings and genre
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human-melanoma cells
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n-linked glycosylation
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mutant p53
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wild-type
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inhibition
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gene
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apoptosis
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mutation
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lines
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mechanisms
Added entries (persons, corporate bodies, meetings, titles ...)
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Girnita, A.Karolinska Institutet
(author)
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Brodin, B.Karolinska Institutet
(author)
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Xie, Y. T.
(author)
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Nilsson, G.Karolinska Institutet
(author)
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Dricu, A.
(author)
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Lundeberg, JoakimKTH,Bioteknologi(Swepub:kth)u1qkn9kw
(author)
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Wejde, J.Karolinska Institutet
(author)
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Bartolazzi, A.Karolinska Institutet
(author)
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Wiman, K. G.Karolinska Institutet
(author)
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Larsson, O.Karolinska Institutet
(author)
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Karolinska InstitutetBioteknologi
(creator_code:org_t)
Related titles
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In:Cancer Research60:18, s. 5278-52830008-54721538-7445
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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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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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- Articles in the publication
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Cancer Research
- By the university
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Royal Institute of Technology
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Karolinska Institutet