Constitutive expression of the Id1 gene impairs mouse B cell development

Sun, Xiao Hong

doi:10.1016/0092-8674(94)90078-7

Cited by 243 publications

(179 citation statements)

References 56 publications

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“…1,10 -12 Their expression is enhanced during cellular proliferation and in response to mitogenic stimuli, 19,31 and overexpression of Id genes inhibits differentiation and/or enhances proliferation in several different cell types. 15,[32][33][34] The forced expression of Id-1 in mouse small intestinal epithelium results in adenoma formation in these animals. 35 The growth-promoting effects of Id genes are thought to occur through several mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Id-1 and Id-2 Are Overexpressed in Pancreatic Cancer and in Dysplastic Lesions in Chronic Pancreatitis

Maruyama

Kleeff

Wildi

et al. 1999

The American Journal of Pathology

138

113

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Id proteins antagonize basic helix-loop-helix proteins , inhibit differentiation , and enhance cell proliferation. In this study we compared the expression of Id-1 , Id-2 , and Id-3 in the normal pancreas , in pancreatic cancer , and in chronic pancreatitis (CP). Northern blot analysis demonstrated that all three Id mRNA species were expressed at high levels in pancreatic cancer samples by comparison with normal or CP samples. Pancreatic cancer cell lines frequently coexpressed all three Ids , exhibiting a good correlation between Id mRNA and protein levels , as determined by immunoblotting with highly specific anti-Id antibodies. Immunohistochemistry using these antibodies demonstrated the presence of faint Id-1 and Id-2 immunostaining in pancreatic ductal cells in the normal pancreas , whereas Id-3 immunoreactivity ranged from weak to strong. In the cancer tissues, Basic helix-loop-helix (bHLH) proteins play an important role as transcription factors in cellular development, proliferation, and differentiation. 1,2 The basic domain of the bHLHs is required for binding to an E-box DNA sequence, thus promoting transcription of specific target genes. The HLH domain promotes dimer formation with various members of the bHLH protein family. 1,2 Homodimers of the class B family of bHLH proteins, including MyoD, NeuroD, and numerous other proteins, are known to activate tissue-specific genes. 3-5 These tissuespecific bHLHs typically form heterodimers with widely expressed class A bHLHs, which include proteins encoded by E2A, E2-2, HEB, and other genes (also termed E-proteins). 6 -9 These heterodimers activate transcription of genes that are associated with differentiation.Id genes encode a family of four HLH proteins that lack the basic DNA binding domain. 1,10 They act as dominantnegative HLH proteins by forming high affinity heterodimers with other bHLH proteins, thereby preventing them from binding to DNA and inhibiting transcription of differentiation-associated genes. 10 -12 Id gene expression is down-regulated on differentiation in many cell types in vitro and in vivo. [13][14][15][16][17][18] In addition, Id proteins seem to be required for cell cycle progression through G 1 /S phase in certain cell types, and interaction between Id-2 and pRB is associated with enhanced proliferation in some cell lines in vitro. 19 -23 Pancreatic cancer is the fifth leading cause of cancer death in the United States, with a mortality rate that virtually equals its incidence rate. 24 This malignancy is often associated with the overexpression of a variety of mitogenic growth factors and their receptors, and by oncogenic mutations of K-ras and inactivation of the p53 tumor suppressor gene. 25 We have recently reported that pancreatic cancers overexpress the HLH protein Id-2, and that enhanced expression of this protein is evident in the cytoplasm of the cancer cells within the pancreatic tumor mass. 26 It is not known, however, whether the expression of other Id proteins is altered in this malignancy, or whether their expressio...

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Section: Discussionmentioning

confidence: 99%

Id-1 and Id-2 Are Overexpressed in Pancreatic Cancer and in Dysplastic Lesions in Chronic Pancreatitis

Maruyama

Kleeff

Wildi

et al. 1999

The American Journal of Pathology

138

113

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“…The Id proteins are helix-loop-helix (HLH) proteins that act as dominant inhibitors of basic HLH transcription factors, by forming transcriptionally inactive heterodimers (Norton et al, 1998). Id proteins have been reported to inhibit the di erentiation of several types of cells, including B lymphocytes (Sun, 1994) and myeloid cells (Kreider et al 1992). It has been argued that their down-regulation is necessary for cells to di erentiate (although exceptions have been reported).…”

Section: The Igf-ir In Differentiationmentioning

confidence: 99%

The contradictions of the insulin-like growth factor 1 receptor

2000

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“…Overexpression studies of Id proteins in several in vivo systems have also been carried out (Sun, 1994;Martinsen and Bronner-Fraser, 1998;Wice and Gordon, 1998;Morrow et al, 1999;Kim et al, 1999;Cai et al, 2000). Phenotypes detected in both gain-of-function and loss-of-function experiments give us insight into potential bHLH proteins as well as regulatory roles of Id proteins in the respective organ development.…”

Section: Introductionmentioning

confidence: 99%

Id and development

2001

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During development, it is obvious that enormous multiplication and diversi®cation of cells is required to build a body plan from a single fertilized egg and that these two processes, proliferation and di erentiation, must be coordinated properly. Id proteins, negative regulators of basic helix ± loop ± helix transcription factors, possess the ability to inhibit di erentiation and to stimulate proliferation, and are useful molecules for investigating the mechanisms regulating development. In the past few years, our understanding of the roles of Id proteins has been substantially enhanced by the detailed investigation of genetically modi®ed animals. The data have indicated that the functions of Id proteins in vivo are functionally related to those revealed by earlier work in cell culture systems. However, unexpected organs and cell types have also been found to require Id proteins for their normal development. This review looks at the advances made in our understanding of the in vivo functions of Id proteins. The topics discussed include neurogenesis, natural killer cell development, lymphoid organogenesis, mammary gland development and spermatogenesis. Oncogene (2001) 20, 8290 ± 8298

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Constitutive expression of the Id1 gene impairs mouse B cell development

Cited by 243 publications

References 56 publications

Id-1 and Id-2 Are Overexpressed in Pancreatic Cancer and in Dysplastic Lesions in Chronic Pancreatitis

Id-1 and Id-2 Are Overexpressed in Pancreatic Cancer and in Dysplastic Lesions in Chronic Pancreatitis

The contradictions of the insulin-like growth factor 1 receptor

Id and development

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