Alteration of c-fos gene methylation in human gliomas

Uyeno, Shinji; Komura, Jun‐ichiro; Tawa, Riichi; Aoki, Yasuhiro; Nata, Masayuki; Sasano, Hironobu; Nakura, Hiroshi; Sagisaka, Kaoru; Kayama, Takamasa; Yoshimoto, Takashi; Ono, Tetsuya

doi:10.1002/(sici)1098-2744(199606)16:2<91::aid-mc5>3.0.co;2-q

Cited by 6 publications

(5 citation statements)

References 43 publications

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“…Our data, specifically those from cases #5 and 6, informative for both IGF2 and H19, thus suggest independent transcriptional regulation of these two genes in breast tissue, in contrast to a proposed regionally controlled regulation of IGF2 and H19 expression [13]. Although this ‘enhancer competition model’ is supported by the observations of several studies in mice ([9]for review), also less compatible data are emerging suggesting, like our study, that the allele‐specific transcriptional regulation of these two genes is not as closely linked as previously assumed [22, 28, 29].…”

Section: Resultssupporting

confidence: 55%

Loss of imprinting of IGF2 and not H19 in breast cancer, adjacent normal tissue and derived fibroblast cultures

et al. 1998

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Insulin-like growth factors are involved in the paracrine growth regulation of human breast tumor cells. IGF2 is imprinted in most tissues, and shows expression of the paternal allele only. To investigate whether disruption of this monoallelic IGF2 expression is involved in breast cancer development, a series of primary tumors and adjacent, histologically normal, breast tissue samples, as well as matched primary in vitro fibroblast cultures were studied. Biallelic expression (partial) of IGF2 was found in the majority of in vivo samples, and corresponding fibroblast cultures, while monoallelic expression was found in a normal breast sample. In contrast, H19, a closely apposed, but reciprocally imprinted gene, assumed to be regulated by a common control element, showed retention of monoallelic H19 expression in all in vivo and in the majority of in vitro samples. These data indicate that IGF2, but not H19, is prone to loss of imprinting in breast cancer.z 1998 Federation of European Biochemical Societies.

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Section: Resultssupporting

confidence: 55%

Loss of imprinting of IGF2 and not H19 in breast cancer, adjacent normal tissue and derived fibroblast cultures

et al. 1998

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“…The incidence of LOI is similar to those reported in di erent adult neoplasms Kondo et al, 1995;Suzuki et al, 1994;Wu et al, 1997) but is slightly lower than that found in other carcinomas (McCann et al, 1996;Nonomura et al, 1997;Oda et al, 1998;Rainier et al, 1993). Although we cannot completely exclude the possibility that this epigenetic event might be a manifestation of a genome-wide breakdown, our data and those of others, indicate that LOI is a nonrandom and specific aberration associated with the development of HNSC and other tumors (Reik et al, 1995a,b;Uyeno et al, 1996).…”

Section: Discussioncontrasting

confidence: 59%

Frequent loss of imprinting at the IGF2 and H19 genes in head and neck squamous carcinoma

et al. 1999

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Genomic imprinting is an inherited epigenetic phenomenon that results in parental ± origin ± speci®c gene expression in somatic cells. Relaxation or loss of this feature in certain genes has been demonstrated in several pediatric and adult neoplasms, suggesting an association with tumorigenesis. We analysed 64 primary untreated head and neck squamous carcinoma for the loss of imprinting in the IGF2 and H19 genes to determine the implications of this alteration in the development and progression of these tumors. Forty-nine (77%) of the 64 tumors were informative for imprinting analyses of these genes. IGF2 and H19 were imprinted in all normal squamous epithelium examined. Twelve (37.5%) of 32 tumors informative for H19 and 11 (40.7%) of 27 tumors informative for IGF2 manifested loss of imprinting. Ten tumors were informative for both genes, of which four maintained the constitutional imprinting and six showed loss of imprinting at either H19 or IGF2. These data suggest that loss of imprinting at the IGF2 and H19 loci play a role in the oncogenesis of head and neck carcinoma.

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“…In mouse models, OE of IGF2 can lead to the development of lung tumors (18,19), loss of IGF2 imprinting promotes development of intestinal tumors (20), and IGF2 has been shown to play an essential role in the induction of medulloblastomas (21). Although previous findings reported loss of imprinting and OE of IGF2 in human meningiomas (22,23), reports on IGF2 expression in glioma have not yielded a consistent picture (24,25).…”

Section: Discussionmentioning

confidence: 99%

Identification of IGF2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma

Soroceanu

Kharbanda

Chen

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Amplification or overexpression of growth factor receptors is a frequent occurrence in malignant gliomas. Using both expression profiling and in situ hybridization, we identified insulin-like growth factor 2 (IGF2) as a marker for a subset of glioblastomas (GBMs) that lack amplification or overexpression of EGF receptor. Among 165 primary high-grade astrocytomas, 13% of grade IV tumors and 2% of grade III tumors expressed IGF2 mRNA levels >50-fold the sample population median. IGF2-overexpressing tumors frequently displayed PTEN loss, were highly proliferative, exhibited strong staining for phospho-Akt, and belonged to a subclass of GBMs characterized by poor survival. Using a serum-free culture system, we discovered that IGF2 can substitute for EGF to support the growth of GBMderived neurospheres. The growth-promoting effects of IGF2 were mediated by the insulin-like growth factor receptor 1 and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of phosphoinositide 3-kinase that shows genomic gains in some highly proliferative GBM cases. PIK3R3 knockdown inhibited IGF2-induced growth of GBM-derived neurospheres. The current results provide evidence that the IGF2-PIK3R3 signaling axis is involved in promoting the growth of a subclass of highly aggressive human GBMs that lack EGF receptor amplification. Our data underscore the importance of the phosphoinositide 3-kinase/Akt pathway for growth of high-grade gliomas and suggest that multiple molecular alterations that activate this signaling cascade may promote tumorigenesis. Further, these findings highlight the parallels between growth factors or receptors that are overexpressed in GBMs and those that support in vitro growth of tumor-derived stem-like cells.astrocytoma ͉ brain tumor ͉ expression profiling ͉ glioma ͉ gliomagenesis

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Alteration of c-fos gene methylation in human gliomas

Cited by 6 publications

References 43 publications

Loss of imprinting of IGF2 and not H19 in breast cancer, adjacent normal tissue and derived fibroblast cultures

Loss of imprinting of IGF2 and not H19 in breast cancer, adjacent normal tissue and derived fibroblast cultures

Frequent loss of imprinting at the IGF2 and H19 genes in head and neck squamous carcinoma

Identification of IGF2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma

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