Targeted deletion of the suppressor gene bin1/amphiphysin2 accentuates the neoplastic character of transformed mouse fibroblasts

Muller, Alexander J.; DuHadaway, James B.; Donover, Preston S.; Sutanto‐Ward, Erika; Prendergast, George C.

doi:10.4161/cbt.3.12.1232

Cited by 25 publications

(28 citation statements)

References 46 publications

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“…4,5,20 Notably, only those Bin1 isoforms capable of nuclear localization are capable of suppressing oncogenic transformation, facilitating cell suicide, and promoting immune escape of transformed cells in mouse model systems. 3,4,8,14,[21][22][23][24][25] Thus, it is conceivable that attenuated expression or nuclear exclusion in breast tumor cells that leads to inactivation of these activities may be sufficient to convey prognostic information for exploitation.…”

Section: Resultsmentioning

confidence: 99%

Bin1 attenuation in breast cancer is correlated to nodal metastasis and reduced survival

Ghaneie¹,

Zemba-Palko²,

Itoh³

et al. 2007

Cancer Biology & Therapy

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Clinical outcomes in breast cancer are likely influenced by modifier genes that affect tumor dormancy versus progression. The Bin1 gene encodes a nucleocytosolic adapter protein that suppresses neoplastic cell transformation and that is often attenuated in human breast carcinoma. Recent mouse genetic studies indicate that Bin1 loss cooperates with ras activation to drive progression of mammary carcinoma, establishing Bin1 as a negative modifier of tumor progression in breast cancer. In this study, we investigated whether immunohistochemical losses of nuclear Bin1 proteins in cases of human breast cancer were correlated to progression status. In American and Japanese groups of low or middle grade breast cancers, losses were associated with reduced survival and increased nodal metastasis, respectively. Taken together with recent findings from mouse genetic studies, these findings encourage further evaluation of the potential utility of Bin1 as a clinical prognostic marker in breast cancer.

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Section: Resultsmentioning

confidence: 99%

Bin1 attenuation in breast cancer is correlated to nodal metastasis and reduced survival

Ghaneie¹,

Zemba-Palko²,

Itoh³

et al. 2007

Cancer Biology & Therapy

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“…IDO elevation in Bin1 -/-cells depends on increased NF-kB and STAT activity, based on the ability of inhibitors of these transcription factors to phenocopy Bin1 action. These observations imply that Bin1 may limit IDO transcription by restricting the nuclear trafficking or activity of NF-kB and STAT, and some experimental support for this model exists (Bild et al, 2002;Muller et al, 2004). Considering potential intersections with c-Myc, while IDO is not a canonical Myc target gene, it is interesting that transcriptional activation by NF-kB and STAT is antagonized by c-Myc.…”

Section: Ido Is a Key Regulatory Target For Cancer Suppression Gene Bin1mentioning

confidence: 99%

Immune escape as a fundamental trait of cancer: focus on IDO

2008

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Immune escape is a critical gateway to malignancy. The emergence of this fundamental trait of cancer represents the defeat of immune surveillance, a potent, multi-armed and essential mode of cancer suppression that may influence the ultimate clinical impact of an early stage tumor. Indeed, immune escape may be a central modifier of clinical outcomes, by affecting tumor dormancy versus progression, licensing invasion and metastasis and impacting therapeutic response. Although relatively little studied until recently, immune suppression and escape in tumors are now hot areas with clinical translation of several new therapeutic agents already under way. The interconnections between signaling pathways that control immune escape and those that control proliferation, senescence, apoptosis, metabolic alterations, angiogenesis, invasion and metastasis remain virtually unexplored, offering rich new areas for investigation. Here, an overview of this area is provided with a focus on the tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDO) and its recently discovered relative IDO2 that are implicated in suppressing T-cell immunity in normal and pathological settings including cancer. Emerging evidence suggests that during cancer progression activation of the IDO pathway might act as a preferred nodal modifier pathway for immune escape, for example analogous to the PI3K pathway for survival or the VEGF pathway for angiogenesis. Small molecule inhibitors of IDO and IDO2 heighten chemotherapeutic efficacy in mouse models of cancer in a nontoxic fashion and an initial lead compound entered phase I clinical trials in late 2007. New modalities in this area offer promising ways to broaden the combinatorial attack on advanced cancers, where immune escape mechanisms likely provide pivotal support.

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“…Likewise, the ubiquitously expressed Bin1 splice isoforms, which encode its anticancer properties, have been implicated in both endosomal trafficking and transcriptional repression (21,22). The possibility that Bin1 adapter proteins may affect pathways leading to the nucleus has garnered additional support based on possible involvement in the trafficking of signal transducer and activator of transcription (STAT) and nuclear factor-nB (NF-nB) transcription factors (23,24). Studies aimed at understanding how Bin1 restricts tumor outgrowth identified immune tolerance established through IDO deregulation as a likely mechanistic explanation (25).…”

Section: Immune Escape In Cancer: Modulation Of Indoleamine-23 Dioxymentioning

confidence: 99%

Marrying Immunotherapy with Chemotherapy: Why Say IDO?

2005

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Activation of the tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) in cancer cells facilitates immune escape. A recent study now shows how smallmolecule inhibitors of IDO can be used to leverage the efficacy of traditional chemotherapeutic drugs that are used to treat cancer in the clinic. By promoting antitumor immune responses in combination with cytotoxic chemotherapy, IDO inhibitors may offer a drug-based strategy to more effectively attack systemic cancer. (Cancer Res 2005; 65(18): 8065-8)

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Targeted deletion of the suppressor gene bin1/amphiphysin2 accentuates the neoplastic character of transformed mouse fibroblasts

Cited by 25 publications

References 46 publications

Bin1 attenuation in breast cancer is correlated to nodal metastasis and reduced survival

Bin1 attenuation in breast cancer is correlated to nodal metastasis and reduced survival

Immune escape as a fundamental trait of cancer: focus on IDO

Marrying Immunotherapy with Chemotherapy: Why Say IDO?

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