NF1 Tumor Suppressor Gene Function

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NF1 Tumor Suppressor Gene Function Narrowing the GAP

tumor suppressor gene, loss of heterozygosity (LOH) or Introduction “second-hit” somatic mutations in the inherited wildTumor suppressor genes are typically identified through type allele have been detected in some tumor types in their association with a familial cancer syndrome. As a NF1 patients (Xu et al., 1992; Legius et al., 1993; Shannon result, information regarding the normal function o...

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The NF1 tumor suppressor critically regulates TSC2 and mTOR.

Loss-of-function mutations in the NF1 tumor suppressor gene underlie the familial cancer syndrome neurofibromatosis type I (NF1). The NF1-encoded protein, neurofibromin, functions as a Ras-GTPase activating protein (RasGAP). Accordingly, deregulation of Ras is thought to contribute to NF1 development. However, the critical effector pathways involved in disease pathogenesis are still unknown. We...

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Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesis.

Intrinsic stress response pathways are frequently mobilized within tumor cells. The mediators of these adaptive mechanisms and how they contribute to carcinogenesis remain poorly understood. A striking example is heat shock factor 1 (HSF1), master transcriptional regulator of the heat shock response. Surprisingly, we found that loss of the tumor suppressor gene neurofibromatosis type 1 (Nf1) in...

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Status of the NF1 tumor suppressor locus in uveal melanoma.

BACKGROUND A clinical association has been observed between uveal melanoma and neurofibromatosis type 1 (NF1). This study aims to determine whether the NF1 tumor suppressor gene is mutated in uveal melanoma. METHODS Thirty-eight uveal melanomas, as well as normal uveal melanocytes, were examined for NF1 deletions by dual-color fluorescence in situ hybridization, and for expression of the NF1 ...

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Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma.

Malignant astrocytoma, the most prevalent primary brain tumor, is resistant to all known therapies and frequently harbors mutations that inactivate p53 and activate Ras signaling. We have generated mouse strains that lack p53 and harbor a conditional allele of the NF1 tumor suppressor that negatively regulates Ras signaling. The mice develop malignant astrocytomas with complete penetrance. The ...

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ژورنال

عنوان ژورنال: Cell

سال: 2001

ISSN: 0092-8674

DOI: 10.1016/s0092-8674(01)00245-8