Sökning: WFRF:(Girnita L)
> (2000-2004) >
Increased expressio...
-
Girnita, L.Karolinska Institutet
(författare)
Increased expression of insulin-like growth factor I receptor in malignant cells expressing aberrant p53 : Functional impact
- Artikel/kapitelEngelska2000
Förlag, utgivningsår, omfång ...
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:kth-20056
-
https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-20056URI
-
http://kipublications.ki.se/Default.aspx?queryparsed=id:1931520URI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
QC 20100525
-
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.
Ämnesord och genrebeteckningar
-
human-melanoma cells
-
n-linked glycosylation
-
mutant p53
-
wild-type
-
inhibition
-
gene
-
apoptosis
-
mutation
-
lines
-
mechanisms
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Girnita, A.Karolinska Institutet
(författare)
-
Brodin, B.Karolinska Institutet
(författare)
-
Xie, Y. T.
(författare)
-
Nilsson, G.Karolinska Institutet
(författare)
-
Dricu, A.
(författare)
-
Lundeberg, JoakimKTH,Bioteknologi(Swepub:kth)u1qkn9kw
(författare)
-
Wejde, J.Karolinska Institutet
(författare)
-
Bartolazzi, A.Karolinska Institutet
(författare)
-
Wiman, K. G.Karolinska Institutet
(författare)
-
Larsson, O.Karolinska Institutet
(författare)
-
Karolinska InstitutetBioteknologi
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Cancer Research60:18, s. 5278-52830008-54721538-7445
Internetlänk
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Girnita, L.
-
Girnita, A.
-
Brodin, B.
-
Xie, Y. T.
-
Nilsson, G.
-
Dricu, A.
-
visa fler...
-
Lundeberg, Joaki ...
-
Wejde, J.
-
Bartolazzi, A.
-
Wiman, K. G.
-
Larsson, O.
-
visa färre...
- Artiklar i publikationen
-
Cancer Research
- Av lärosätet
-
Kungliga Tekniska Högskolan
-
Karolinska Institutet