ABSTRACT
Id proteins, or inhibitors of differentiation/DNA binding, are negative regulators of helix-loop-helix (HLH) type transcription factor, and they can inhibit cell differentiation and promote cell proliferation. Many experiments have proven that high expression of Id proteins in tumors was significantly related to malignant behaviors of tumors, such as tumor invasion and metastasis, suggesting Id proteins can be used to predict the prognosis of tumors. Abnormal expression of Id protein in malignant tumor might be associated with the invasive phenotype and poor prognosis of tumors. Id protein-targeted therapy can effectively inhibit tumor proliferation, invasion and metastasis. This paper reviews the mechanism by which Id protein influences the prognostic factors, such as malignant proliferation, invasion and metastasis, angiogenesis and the researches on progress of related clinical researches.
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Objective To detect the expression of Id1 and p53 in human breast cancer and study their relationship. Methods To choose 80 cases of breast cancer from the surgical department of Tangshan people's hospital. All patients didn't get radiotherapy and chemotherapy before surgery. The expression of Idl and p53 of breast cancer were studied by using SABC immunohistochemistry. Results The expressions of Id1 were found in cytoplasm, while the expression of p53 was found in cell nucleus. The positive rates of Id1 and p53 were 87.5 %(70/80)and 90.0%(72/80) respectively in breast cancer tissues. The expression of Id1 and p53 were significantly higher in breast cancer tissue than those in adjacent non-tumor breast tissues,benign tumor tissues and normal breast tissues(P ＜0.05). The positive rates and expression intensity of Id1 in breast cancer had significant correlation with lymph node metastasis and pTNM stage of the tumor, but had no significant correlation with age, histological differentiation and tumor size. The positive rates and expression intensity of p53 in breast cancer had significant correlation with lymph node metastasis of the tumor, but had no significant correlation with age, histological differentiation,tumor size and pTNM stage. Conclusion Expression of Id1 in human breast cancer is up-regulated. Its expression is associated with lymph node metastasis and TNM stage and represents an independent marker for prognosis of breast cancer. To reduce the expression of Id1 will become the strategy of curing breast cancer. Expression of Id1 and p53 in human breast cancer have the same clinic significance. Each of them can represent an independent marker for prognosis of breast cancer.
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Objective: To study the influence of inhibitor of differentiation 2 (Id2) on cell proliferation and migration in SKOV3 cells, and to investigate the influence of HLH domain deletion in 1d2 gene on SKOV3 cells. Methods: Human ovarian cancer cell line SKOV3 was transfected with pcDNA3.1-Id2, pcDNA3. 1-Id2-DBM and pcDNA3. 1-Id2-DBM-δHLH vectors by SuperFect Transfection Reagent. The cells transfected with blank vector pCDNA3. 1 were used as control. Id2 protein was detected by Western blot, and mRNA transcriptions of Id2, Id2-DBM (D-box mutant), and Id2-DBM-δHLH were measured by RT-PCR. Cell proliferation was assessed by MTT assay. Cell invasion was detected by scratch test and transwell chamber assay. The regulatory effect of Id2 on E-cadherin was evaluated by Western blot. Results: The mRNA and protein levels indicated that the plasmid was successfully transfected. Cell growth curve suggested that the proliferation of cells had no significant difference between each group. Compared with the control group, cell migration ability was significantly enhanced after transfection with pcDNA3. 1-Id2, pcDNA3. 1-Id2-DBM and pcDNA3. 1-Id2-DBM-δHLH vectors. The downregulation of E-cadherin protein was accompanied with increased migration capability in pcDNA3. 1-Id2-DBM and pcDNA3. 1-Id2-DBM-δHLH vectors-transfected cells. Conclusion: Overexpression of Id2 promotes the migration capability of SKOV3 cells, which might be related with the downregulation of E-cadherin. The action still exists after the HLH domain deletion in Id2 gene.
ABSTRACT
The ubiquitously expressed family of Id(inhibitor of differentiation) helix-loop-helix(HLH) proteins function as dominant negative regulators of basic HLH (bHLH) transcriptional regulators. In eukaryotic organisms, Id proteins have been implicated in development, cell differentiation, proliferation, angiogenesis, invasion and migration. Recent studies revealed that Id proteins are not only significantly correlated with cancer progression and prognosis, but also exploited as a tumor therapeutic target. The roles of Id proteins in tumorigenesis were reviewed and the opportunities of Id proteins in cancer targeted therapy were discussed.
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Objective To study the expression of Id mRNA in hematologic malignant tumor cells.Methods The total cellular RNA were extracted from peripheral blood mononuclear cell(PBMC) of the patients with hematologic disorders and health adults as well as from four tumor cell lines(Daudi,Jurkat,K562,U937).The primers based on the reported sequences of Id1,Id2 and Id3 were synthesized.The mRNA expression levels of Id1-Id3 in PBMCs and tumor cells were detected by RT-PCR.Results The mRNA expression of Id1,Id2 and Id3 showed different levels in different cells.Id2 was widely expressed in both normal and malignant cells as well as many types of lymphocyte.The expression levels of Id1 and Id3 mRNA in tumor cells and PBMC from hematologic disorder patients were significantly higher than those in PBMC of healthy adults.Conclusion Different Id genes have different expression patterns in different cell types.It seems that Id1 and Id3 may play some important roles in the proliferation and differentiation of lymphocytes and in the development and growth of tumors.
ABSTRACT
Inhibitors of differentiation(Id) are negative regulators of basic helix-loop-helix(bHLH) type transcription factor.There are four related members of the Id family called Id-1,Id-2,Id-3 and(Id-4) in mammalian cells.Since the identification of Id proteins in 1990,the roles of Id in cell proliferation,differentiation,development,maturation,apoptosis and tumorigenesis have been widely investigated.This article focuses on the role of Id in tumorigenesis.