A census of mammalian imprinting

Morison, Ian M.; Ramsay, Joshua P.; Spencer, Hamish G.

doi:10.1016/j.tig.2005.06.008

Cited by 598 publications

(543 citation statements)

References 61 publications

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“…Our interpretation indicates that the increase in ascl2 expression seen in colorectal cancer cannot be due to loss of imprinting. Such discordance between human and mouse is not an unprecedented; a recent review described 49 transcriptional units with discordant imprinting between mouse and man (Morison et al, 2005). In certain instances the discordance is hypothesized to be due to the absence of a neighbouring imprinted gene or regulator that affects the imprinting of the gene of interest in cis.…”

Section: Discussionmentioning

confidence: 99%

Achaete-scute like 2 (ascl2) is a target of Wnt signalling and is upregulated in intestinal neoplasia

Jubb

Chalasani²,

Frantz³

et al. 2006

Oncogene

121

112

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Achaete-scute like (ASCL)2 is a basic helix-loop-helix transcription factor essential for the maintenance of proliferating trophoblasts during placental development. Using oligonucleotide microarrays we identified ascl2 as a gene significantly upregulated in colorectal adenocarcinomas (n ¼ 36 cancers, n ¼ 16 normals; 15-fold, Po0.0001). This finding was confirmed by quantitative reverse transcriptase (RT)-PCR on large intestinal cancers (n ¼ 29 cancers, n ¼ 16 normals; 10-fold, Po0.0001).In situ hybridization for ascl2 demonstrated expression at the base of small and large intestinal crypts (n ¼ 304), but in no other normal tissues excepting placenta. By in situ hybridization, 52-71% of colorectal adenomas (n ¼ 187), 50-73% of large (n ¼ 327) and 33-64% of small intestinal adenocarcinomas (n ¼ 124) were positive for ascl2 expression. Upregulation of murine ascl2 was also observed using oligonucleotide microarrays, quantitative RT-PCR and in situ hybridization on apc min/ þ and apc 1638N/ þ smad4 À/ þ tumours. Tumour cell lines stably transfected with LEF1 DN or APC2, or transiently transfected with short-interfering RNA (siRNA) against b-catenin showed a significant downregulation of ascl2. Colocalization of ascl2 with nuclear b-catenin was observed in 73 small intestinal adenocarcinomas (P ¼ 0.0008) and apc min/ þ tumours. Preliminary in vitro data suggest ascl2 may promote progression through the G2/M cell cycle checkpoint. In summary, ascl2 is a putative regulator of proliferation that is overexpressed in intestinal neoplasia.

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Section: Discussionmentioning

confidence: 99%

Achaete-scute like 2 (ascl2) is a target of Wnt signalling and is upregulated in intestinal neoplasia

Jubb

Chalasani²,

Frantz³

et al. 2006

Oncogene

121

112

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“…The first such gene to be identified in ovarian and breast cancer was NOEY2/ ARH1 (Yu et al, 1999) and more recently LOT1 (Abdollahi et al, 2003). The recent efforts to map imprinted genes in the mouse genome has contributed to the identification of additional genes that are imprinted, which occur in clusters on chromosomes (Nikaido et al, 2003;Luedi et al, 2005;Morison et al, 2005). RPS6KA2 was not identified as an imprinted gene in any of these screens.…”

Section: Discussionmentioning

confidence: 99%

RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

et al. 2006

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We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative tumour suppressor gene. The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3, RPS6KA2) maps in this interval. It is a serine-threonine kinase that signals downstream of the mitogen-activated protein kinase pathway. It is expressed in normal ovarian epithelium, whereas reduced or absent in tumours or cell lines. We show that RPS6KA2 is monoallelically expressed in the ovary suggesting that loss of a single expressed allele is sufficient to cause complete loss of expression in cancer cells. Further, we have identified two new isoforms of RPS6KA2 with an alternative start codon. Homozygous deletions were identified within the RPS6KA2 gene in two cell lines. Re-expression of RPS6KA2 in ovarian cancer cell lines suppressed colony formation. In UCI101 cells, the expression of RPS6KA2 reduced proliferation, caused G1 arrest, increased apoptosis, reduced levels of phosphorylated extracellular signal-regulated kinase and altered other cell cycle proteins. In contrast, small interfering RNA against RPS6KA2 showed the opposite effect in 41M cells. The above results suggest that RPS6KA2 is a putative tumour suppressor gene to explain allele loss at 6q27.

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“…(9,10) Several imprinted genes play key roles in the regulation of cellular proliferation and growth. (11) Amongst these is the insulin-like growth factor-2 gene (IGF2), one of the bestcharacterized imprinted genes. It is expressed only from the paternal allele and encodes a growth factor involved in fetal and postnatal growth.…”

Section: Introductionmentioning

confidence: 99%

“…(11) This has allowed gene targeting studies in the mouse to unravel the roles of the two ICRs. Particularly, deletion of the H19 ICR resulted in biallelic expression of Igf2 ('loss of imprinting'), when maternally transmitted.…”

Section: Introductionmentioning

confidence: 99%