Requirement of the MASH-1 transcription factor for neuroendocrine differentiation of thyroid C cells

Lanigan, Thomas M.; DeRaad, Shannon K.; Russo, Andrew F.

doi:10.1002/(sici)1097-4695(19980205)34:2<126::aid-neu3>3.0.co;2-4

Cited by 61 publications

(18 citation statements)

References 31 publications

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“…As described [7], [18], expression of LMO3 was highly restricted in adult and fetal brains, and HEN2 was expressed in developing nervous system. Genetic studies demonstrated that HEN2 participates in proper neural crest-derived neuroendocrine development and that Mash1 has a critical role in maintaining neuroendocrine cell phenotype [19], [20]. Although LMO3 -knockout mice did not exhibit any significant developmental defects, mice lacking both LMO1 and LMO3 died after birth, which might be due to neural defects [21].…”

Section: Discussionmentioning

confidence: 99%

Oncogenic LMO3 Collaborates with HEN2 to Enhance Neuroblastoma Cell Growth through Transactivation of Mash1

et al. 2011

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Expression of Mash1 is dysregulated in human neuroblastoma. We have also reported that LMO3 (LIM-only protein 3) has an oncogenic potential in collaboration with neuronal transcription factor HEN2 in neuroblastoma. However, the precise molecular mechanisms of its transcriptional regulation remain elusive. Here we found that LMO3 forms a complex with HEN2 and acts as an upstream mediator for transcription of Mash1 in neuroblastoma. The high levels of LMO3 or Mash1 mRNA expression were significantly associated with poor prognosis in 100 primary neuroblastomas. The up-regulation of Mash1 remarkably accelerated the proliferation of SH-SY5Y neuroblastoma cells, while siRNA-mediated knockdown of LMO3 induced inhibition of growth of SH-SY5Y cells in association with a significant down-regulation of Mash1. Additionally, overexpression of both LMO3 and HEN2 induced expression of Mash1, suggesting that they might function as a transcriptional activator for Mash1. Luciferase reporter assay demonstrated that the co-expression of LMO3 and HEN2 attenuates HES1 (a negative regulator for Mash1)-dependent reduction of luciferase activity driven by the Mash1 promoter. Chromatin immunoprecipitation assay revealed that LMO3 and HEN2 reduce the amount of HES1 recruited onto putative HES1-binding sites and E-box within the Mash1 promoter. Furthermore, both LMO3 and HEN2 are physically associated with HES1 by immunoprecipitation assay. Thus, our present results suggest that a transcriptional complex of LMO3 and HEN2 may contribute to the genesis and malignant phenotype of neuroblastoma by inhibiting HES1 which suppresses the transactivation of Mash1.

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Section: Discussionmentioning

confidence: 99%

Oncogenic LMO3 Collaborates with HEN2 to Enhance Neuroblastoma Cell Growth through Transactivation of Mash1

et al. 2011

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“…Once within the thyroid gland, Mash1 and perhaps RET signaling pathways, are associated with differentiation and the induction of neuronal traits in the cells. In two independent studies, Mash1 null mice are severely impaired in their ability to generate mature C-cells [43,44]. The near or complete absence of C-cells in the Mash1 null mutants suggests progenitors may degenerate before they become differentiated.…”

Section: Tracing the Developmental Origin Of The Thyroid C-cellmentioning

confidence: 99%

Thyroid C-Cell Biology and Oncogenic Transformation

Cote

Grubbs

Hofmann

2015

Recent Results in Cancer Research

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The thyroid parafollicular cell, or commonly named “C-cell,” functions in serum calcium homeostasis. Elevations in serum calcium trigger release of calcitonin from the C-cell, which in turn functions to inhibit absorption of calcium by the intestine, resorption of bone by the osteoclast, and reabsorption of calcium by renal tubular cells. Oncogenic transformation of the thyroid C-cell is thought to progress through a hyperplastic process prior to malignancy with increasing levels of serum calcitonin serving as a biomarker for tumor burden. The discovery that Multiple Endocrine Neoplasia, type 2 is caused by activating mutations of the RET gene serves to highlight the RET-RAS-MAPK signaling pathway in both initiation and progression of medullary thyroid carcinoma. Thyroid C-cells are known to express RET at high levels relative to most cell types, therefore aberrant activation of this receptor is targeted primarily to the C-cell, providing one possible cause of tissue-specific oncogenesis. The role of RET signaling in normal C-cell function is unknown though calcitonin gene transcription appears to be sensitive to RET activation. Beyond RET the modeling of oncogenesis in animals and screening of human tumors for candidate gene mutations has uncovered mutation of RAS family members and inactivation of Rb1 regulatory pathway as potential mediators of C-cell transformation. A growing understanding of how RET interacts with these pathways, both in normal C-cell function and during oncogenic transformation will help in the development of novel molecular targeted therapies.

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“…This results in the activation of multiple target genes such as hairy enhancer of split 1 (HES-1), which in turn controls the expression of Achaete Scute Complex-Like 1 (ASCL-1) (27). ASCL-1 has been shown to play a role in the development of pulmonary neuroendocrine cells, thyroid C cells, and adrenal chromaffin cells and is decreased when Notch signaling is active (30, 31). …”

Section: Notch-1 Signaling Pathwaymentioning

confidence: 99%

Signaling Mechanisms in Neuroendocrine Tumors as Targets for Therapy

Zarebczan

Chen

2010

Endocrinology and Metabolism Clinics of North America

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Although neuroendocrine tumors are rare, the more common types such as gastrointestinal and pancreatic carcinoids, medullary thyroid cancers, and small cell lung cancers have been studied in detail over the last few years. Published data thus far indicates that multiple signaling pathways are involved in these cancers. Recent focus has been on developing novel therapeutics by targeting specific signaling pathways. This paper will detail several of the signaling mechanisms that have been discovered to play a role in the development and progression of neuroendocrine tumors. The therapeutic options developed to address the various pathways, including their specific mechanisms of actions will also be discussed.

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Requirement of the MASH-1 transcription factor for neuroendocrine differentiation of thyroid C cells

Cited by 61 publications

References 31 publications

Oncogenic LMO3 Collaborates with HEN2 to Enhance Neuroblastoma Cell Growth through Transactivation of Mash1

Oncogenic LMO3 Collaborates with HEN2 to Enhance Neuroblastoma Cell Growth through Transactivation of Mash1

Thyroid C-Cell Biology and Oncogenic Transformation

Signaling Mechanisms in Neuroendocrine Tumors as Targets for Therapy

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