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Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that is inversely correlated with functional PTEN

Packer, Leisl ; Pavey, Sandra ; Parker, Andrew ; Stark, Mitchell ; Johansson, Peter ; Clarke, Belinda ; Pollock, Pamela ; Ringnér, Markus LU orcid and Hayward, Nicholas (2006) In Carcinogenesis 27(9). p.1778-1786
Abstract
The tumor suppressor PTEN antagonizes phosphatidylinositol 3-kinase (PI3K), which contributes to tumorigenesis in many cancer types. While PTEN mutations occur in some melanomas, their precise mechanistic consequences have yet to be elucidated. We sought to identify novel downstream effectors of PI3K using a combination of genomic and functional tests. Microarray analysis of 53 melanoma cell lines identified 610 genes differentially expressed (P < 0.05) between wild-type lines and those with PTEN aberrations. Many of these genes are known to be involved in the PI3K pathway and other signaling pathways influenced by PTEN. Validation of differential gene expression by qRT-PCR was performed in the original 53 cell lines and an independent... (More)
The tumor suppressor PTEN antagonizes phosphatidylinositol 3-kinase (PI3K), which contributes to tumorigenesis in many cancer types. While PTEN mutations occur in some melanomas, their precise mechanistic consequences have yet to be elucidated. We sought to identify novel downstream effectors of PI3K using a combination of genomic and functional tests. Microarray analysis of 53 melanoma cell lines identified 610 genes differentially expressed (P < 0.05) between wild-type lines and those with PTEN aberrations. Many of these genes are known to be involved in the PI3K pathway and other signaling pathways influenced by PTEN. Validation of differential gene expression by qRT-PCR was performed in the original 53 cell lines and an independent set of 18 melanoma lines with known PTEN status. Osteopontin (OPN), a secreted glycophosphoprotein that contributes to tumor progression, was more abundant at both the mRNA and protein level in PTEN mutants. The inverse correlation between OPN and PTEN expression was validated (P < 0.02) by immunohistochemistry using melanoma tissue microarrays. Finally, treatment of cell lines with the PI3K inhibitor LY294002 caused a reduction in expression of OPN. These data indicate that OPN acts downstream of PI3K in melanoma and provides insight into how PTEN loss contributes to melanoma development. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Carcinogenesis
volume
27
issue
9
pages
1778 - 1786
publisher
Oxford University Press
external identifiers
  • pmid:16571650
  • wos:000239901000006
  • scopus:33747887710
  • pmid:16571650
ISSN
0143-3334
DOI
10.1093/carcin/bgl016
language
English
LU publication?
yes
id
7ed9dbd1-1e5c-4740-863e-6677d99755b1 (old id 397556)
date added to LUP
2016-04-01 12:32:24
date last changed
2021-08-18 05:33:17
@article{7ed9dbd1-1e5c-4740-863e-6677d99755b1,
  abstract     = {The tumor suppressor PTEN antagonizes phosphatidylinositol 3-kinase (PI3K), which contributes to tumorigenesis in many cancer types. While PTEN mutations occur in some melanomas, their precise mechanistic consequences have yet to be elucidated. We sought to identify novel downstream effectors of PI3K using a combination of genomic and functional tests. Microarray analysis of 53 melanoma cell lines identified 610 genes differentially expressed (P &lt; 0.05) between wild-type lines and those with PTEN aberrations. Many of these genes are known to be involved in the PI3K pathway and other signaling pathways influenced by PTEN. Validation of differential gene expression by qRT-PCR was performed in the original 53 cell lines and an independent set of 18 melanoma lines with known PTEN status. Osteopontin (OPN), a secreted glycophosphoprotein that contributes to tumor progression, was more abundant at both the mRNA and protein level in PTEN mutants. The inverse correlation between OPN and PTEN expression was validated (P &lt; 0.02) by immunohistochemistry using melanoma tissue microarrays. Finally, treatment of cell lines with the PI3K inhibitor LY294002 caused a reduction in expression of OPN. These data indicate that OPN acts downstream of PI3K in melanoma and provides insight into how PTEN loss contributes to melanoma development.},
  author       = {Packer, Leisl and Pavey, Sandra and Parker, Andrew and Stark, Mitchell and Johansson, Peter and Clarke, Belinda and Pollock, Pamela and Ringnér, Markus and Hayward, Nicholas},
  issn         = {0143-3334},
  language     = {eng},
  number       = {9},
  pages        = {1778--1786},
  publisher    = {Oxford University Press},
  series       = {Carcinogenesis},
  title        = {Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that is inversely correlated with functional PTEN},
  url          = {http://dx.doi.org/10.1093/carcin/bgl016},
  doi          = {10.1093/carcin/bgl016},
  volume       = {27},
  year         = {2006},
}