Mitogen‐inducible gene 6 (MIG‐6), adipophilin and tuftelin are inducible by hypoxia

Saarikoski, Sirkku T.; Rivera, Steven; Hankinson, Oliver

doi:10.1016/s0014-5793(02)03475-0

Cited by 76 publications

(64 citation statements)

References 22 publications

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“…We conclude that loss of RALT signalling complements ERBB2 gene amplification: dramatic overexpression of ErbB-2 promotes its constitutive activation, while removal of RALT is permissive for unabated propagation of ErbB-2 oncogenic signals. Moreover, as RALT transcription is promiscuously induced by many extracellular stimuli, including hormones, growth factors and stress (Makkinje et al, 2000;Fiorini et al, 2002;Saarikoski et al, 2002), loss of RALT expression renders ErbB-2 oncogenic signalling resilient to cross-regulation by extracellular cues.…”

Section: Discussionmentioning

confidence: 99%

Loss of RALT/MIG-6 expression in ERBB2-amplified breast carcinomas enhances ErbB-2 oncogenic potency and favors resistance to Herceptin

Anastasi¹,

et al. 2005

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An emerging paradigm holds that loss of negative signalling to receptor tyrosine kinases (RTKs) is permissive for their oncogenic activity. Herein, we have addressed tumor suppression by RALT/MIG-6, a transcriptionally controlled feedback inhibitor of ErbB RTKs, in breast cancer cells. Knockdown of RALT expression by RNAi enhanced the EGF-dependent proliferation of normal breast epithelial cells, indicating that loss of RALT signalling in breast epithelium may represent an advantageous condition during ErbB-driven tumorigenesis. Although mutational inactivation of the RALT gene was not detected in human breast carcinomas, RALT mRNA and protein expression was strongly and selectively reduced in ERBB2-amplified breast cancer cell lines. Reconstitution of RALT expression in ERBB2-amplified SKBr-3 and BT474 cells inhibited ErbB-2-dependent mitogenic signalling and counteracted the ability of ErbB ligands to promote resistance to the ErbB-2-targeting drug Herceptin. Thus, loss of RALT expression cooperates with ERBB2 gene amplification to drive full oncogenic signalling by the ErbB-2 receptor. Moreover, loss of RALT signalling may adversely affect tumor responses to ErbB-2-targeting agents.

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Section: Discussionmentioning

confidence: 99%

Loss of RALT/MIG-6 expression in ERBB2-amplified breast carcinomas enhances ErbB-2 oncogenic potency and favors resistance to Herceptin

Anastasi¹,

et al. 2005

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“…Mig-6 is an immediate early response gene that can be induced by various mitogens and commonly occurring chronic stress stimuli (16)(17)(18). Mig-6 is an adaptor molecule containing a CRIB domain, a src homology 3 (SH3) binding domain, a 14-3-3 binding domain, and an epidermal growth factor receptor (EGFR) binding domain (19,20).…”

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confidence: 99%

Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease

Jeong

Lee

et al. 2009

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

118

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Normal endometrial function requires a balance of progesterone (P4) and estrogen (E2) effects. An imbalance caused by increased E2 action and/or decreased P4 action can result in abnormal endometrial proliferation and, ultimately, endometrial adenocarcinoma, the fourth most common cancer in women. We have identified mitogen-inducible gene 6 (Mig-6) as a downstream target of progesterone receptor (PR) and steroid receptor coactivator (SRC-1) action in the uterus. Here, we demonstrate that absence of Mig-6 in mice results in the inability of P4 to inhibit E2-induced uterine weight gain and E2-responsive target genes expression. At 5 months of age, the absence of Mig-6 results in endometrial hyperplasia. Ovariectomized Mig-6 d/d mice exhibit this hyperplastic phenotype in the presence of E2 and P4 but not without ovarian hormone. Ovariectomized Mig-6 d/d mice treated with E2 developed invasive endometrioid-type endometrial adenocarcinoma. Importantly, the observation that endometrial carcinomas from women have a significant reduction in MIG-6 expression provides compelling support for an important growth regulatory role for Mig-6 in the uterus of both humans and mice. This demonstrates the Mig-6 is a critical regulator of the response of the endometrium to E2 in regulating tissue homeostasis. Since Mig-6 is regulated by both PR and SRC-1, this identifies a PR, SRC-1, Mig-6 regulatory pathway that is critical in the suppression of endometrial cancer.estrogen ͉ endometrial cancer ͉ progesterone ͉ progesterone receptor ͉ SRC-1

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“…The biological relevance of 4 newly identified genes to hypoxia and pulmonary hypertension was suggested by an automated biomedical literature search. The subsequent manual evaluation of PubMatrix citations confirmed involvement of Mig6, F3, Bmp6, and Ndrg1 genes in hypoxia-triggered response [15][16][17][18][19]. Up-regulation of Mig6 expression was validated by real-time RT-PCR.…”

Section: Discussionmentioning

confidence: 79%

“…This approach identified several hypoxia-related genes that were missed by regular SAM analysis, including the mouse Mig6 gene ( Table 1). Involvement of Mig6 in response to experimental hypoxia [17] is well documented, however, the standard SAM analysis of an underpowered hypoxia experiment failed to identify a significant transcriptional response of this gene to hypoxia (Table 1). We speculated that this was mainly due to a limited number of expression profiles (2 control and 2 hypoxia arrays) and hypothesized that the discriminating power of transcriptional changes can be improved by the group analysis of probe-sets that hybridize to the same transcript.…”

Section: Discussionmentioning

confidence: 99%

“…Transcriptional changes detected by 26 exon-sharing probe-sets ( Figure 1B) were compared to those detected by the rest of the target-sharing probe-sets (63 probe-sets, Figure 1C) and demonstrated higher correlation of transcriptional changes detected by the exon-sharing probe-sets. The PubMatrix automated biomedical literature search of 24 recovered ( Figure 1A) candidate genes identified several well-known hypoxia or pulmonary hypertension-related genes (Table 1), including Mig6, F3, Bmp6, and Ndrg1 [15][16][17][18][19]. The mouse Mig6 gene was selected for further validation.…”

Section: Gene Expression Analysis Of Target-sharing Probe-setsmentioning

confidence: 99%

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Exon-based mapping of microarray probes: Recovering differential gene expression signal in underpowered hypoxia experiment

Grigoryev

Fan

Shimoda

et al. 2007

Molecular and Cellular Probes

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There is an immense collection of underpowered Affymetrix gene array experiments. Although a majority of these experiments generated biologically feasible results, the considerable fraction of assays failed to identify expected transcriptional changes. There is an unused potential of Affymetrix probe-set redundancy for common exonic and UTR regions. We hypothesized that group analysis of multiple probe-sets which hybridize to the same exon or UTR will increase array discriminating power of transcriptional changes. To test this hypothesis, we analyzed Affymetrix mouse probe-sets that share the same exon using blocking feature of the Significance Analysis of Microarrays (SAM). Two-thousand two-hundred one exon-sharing probe-sets targeting 1,011 transcripts were identified by mapping 36701 MG-U74v2 probe-sets to genomic alignments of 3,971,086 known mouse transcripts. Using the blocking feature of SAM with an underpowered (two microarrays per experimental condition) mouse hypoxia-induced pulmonary hypertension model, we identified 24 genes that were significantly (FDR<5%) affected by hypoxia but were not detected by regular SAM. The relevance of the four newly identified genes (Mig6, F3, Bmp6, and Ndrg1) to known hypoxiaassociated responses was confirmed by PubMatrix; and hypoxia-induced up-regulation of Mig6 expression was validated by real-time RT-PCR. We demonstrated that analysis of exon-sharing probe-sets allowed discovery of additional hypoxia-affected genes in an underpowered array experiment. This method will facilitate re-evaluation of existing underpowered Affymetrix gene expression profiles.

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Mitogen‐inducible gene 6 (MIG‐6), adipophilin and tuftelin are inducible by hypoxia

Cited by 76 publications

References 22 publications

Loss of RALT/MIG-6 expression in ERBB2-amplified breast carcinomas enhances ErbB-2 oncogenic potency and favors resistance to Herceptin

Loss of RALT/MIG-6 expression in ERBB2-amplified breast carcinomas enhances ErbB-2 oncogenic potency and favors resistance to Herceptin

Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease

Exon-based mapping of microarray probes: Recovering differential gene expression signal in underpowered hypoxia experiment

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