Id-1 and Id-2 Proteins as Molecular Markers for Human Prostate Cancer Progression

Coppé, Jean‐Philippe; Itahana, Yoko; Moore, Dan H.; Bennington, James L.; Desprez, Pierre-Yves

doi:10.1158/1078-0432.ccr-03-0933

Cited by 101 publications

(121 citation statements)

References 27 publications

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“…Overexpression of Id-1 promotes mammary epithelial cell invasion (Desprez et al, 1998), and reduced expression of Id-1 in metastatic breast cancer cells leads to a decrease in invasiveness in vitro (Fong et al, 2003). Overexpression of Id-1 in prostate cancer cells also promotes metastasis through increased angiogenesis and invasiveness (Coppe et al, 2004). Reduced expressions of Id-1 and Id-3 have been demonstrated to inhibit the metastatic ability of gastric cancer cells (Tsuchiya et al, 2005), and Id-1 expression has been shown to be associated with the presence of invasion in endometrial carcinoma (Takai et al, 2001) and tumour angiogenesis in human pancreatic cancer (Lee et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…These results suggested that Id-2 promotes neoplastic transformation of oesophageal epithelial cells. Id-2 has been shown to bind and inhibit the function of retinoblastoma protein, a tumour suppressor protein (Iavarone et al, 1994;Lasorella et al, 1996) and therefore has been implicated in tumour progression in several cancer types (Maruyama et al, 1999;Fukuma et al, 2003;Coppe et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

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Id-1 and Id-2 are markers for metastasis and prognosis in oesophageal squamous cell carcinoma

Chan

et al. 2007

Br J Cancer

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Id protein family consists of four members namely Id-1 to Id-4. Different from other basic helix -loop -helix transcription factors, they lack the DNA binding domain. Id proteins have been shown to be dysregulated in many different cancer types and their prognostic value has also been demonstrated. Recently, Id-1 has been shown to be upregulated in oesophageal squamous cell carcinoma (ESCC). However, the prognostic implications of Id proteins in ESCC have not been reported. We examined the expression of the Id proteins in ESCC cell lines and clinical ESCC specimens and found that Id protein expressions were dysregulated in both the ESCC cell lines and specimens. By correlating the expression levels of Id proteins and the clinicopathological data of our patient cohort, we found that M1 stage tumours had significantly higher nuclear Id-1 expression (P ¼ 0.012) while high nuclear Id-1 expression could predict development of distant metastasis within 1 year of oesophagectomy (P ¼ 0.005). In addition, high levels of Id-2 expression in both cytoplasmic and nuclear regions predicted longer patient survival (P ¼ 0.041). Multivariate analysis showed that high-level expression of Id-2 in both cytoplasmic and nuclear regions and lower level of nuclear Id-1 expression were independent favourable predictors of survival in our ESCC patients. Our results suggest that Id-1 may promote distant metastasis in ESCC, and both Id-1 and Id-2 may be used for prognostication for ESCC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Id-1 and Id-2 are markers for metastasis and prognosis in oesophageal squamous cell carcinoma

Chan

et al. 2007

Br J Cancer

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“…Using a commercially available antibody, elevated Id1 protein expression levels have been reported in diverse human cancers, including epithelial malignancies of ovary, colon, pancreas, nasopharynx, stomach, and esophagus; in neural tumors; melanomas; Ewing's sarcoma; seminoma; leukemia; and, more recently, bladder transitional cell carcinoma (1,5). Previous studies in prostate cancer found intense immunoreactivity in some tumor cells and related this to a poorer prognosis (4,6). Similarly, studies in mammary cancers found that a majority of the tumors showed some level of Id1 protein expression (3).…”

Section: Discussionmentioning

confidence: 99%

“…The expression and role of the Id1 protein in epithelial cancer cells, however, is controversial. For example, some investigators have reported that the neoplastic cells of breast, prostate, and bladder carcinomas express the Id1 protein, and that this finding correlates in some cases with poor prognosis (3)(4)(5)(6). Others, however, have reported Id1 protein expression in mammary tumors only in the endothelial cells of blood vessels associated with these lesions (7).…”

Section: Introductionmentioning

confidence: 99%

Reassessment of Id1 Protein Expression in Human Mammary, Prostate, and Bladder Cancers Using a Monospecific Rabbit Monoclonal Anti-Id1 Antibody

et al. 2006

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Id proteins are a class of dominant-negative antagonists of helix-loop-helix transcription factors and have been shown to control differentiation of a variety of cell types in diverse organisms. Although the importance of Id1 in tumor endothelial cells is well established, the expression and role of the Id1 protein in human cancer cells is controversial. To explore this issue, we developed and characterized a highly specific rabbit monoclonal antibody against Id1 to assess its expression in human breast, prostate, and bladder malignancies. Our results show that in usual types of human mammary carcinomas, the Id1 protein is expressed exclusively in the endothelium. Interestingly, we detected nuclear expression of the Id1 protein in the tumor cells in 10 of 45 cases of poorly differentiated and highly aggressive carcinoma with metaplastic morphology. Similarly, only 1 of 30 prostate cancer samples showed Id1-positive tumor cells, whereas in almost all, endothelial cells showed high Id1 expression. Intriguingly, whereas normal prostate glands do not show any Id1 protein expression, basal layer cells of benign prostate glands in proximity to tumors expressed high levels of the Id1 protein.In contrast to the lack of Id1 expression in the usual types of mammary and prostate cancers, the majority of transitional cell bladder tumors showed Id1 protein expression in both tumor and endothelial cells. These results suggest that further refinement of Id1 expression patterns in a variety of tumor types will be necessary to identify and study the functional roles played by Id1 in human neoplastic processes. (Cancer Res 2006; 66(22): 10870-7)

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“…Increased Id-1 expression was detected during carcinogenesis of the prostate in the Noble rat (Ouyang et al, 2001). In human specimens, Id-1 expression in prostate cancer is increased in comparison to benign prostatic hyperplasia specimens (Ouyang et al, 2002a), and increased expression of Id-1 is correlated with Gleason score, reflecting the aggressive nature of Id-1-positive prostate cancers (Ouyang et al, 2002a;Coppe et al, 2004;Yuen et al, 2006). This information suggests that Id-1 is important in both prostate cancer initiation and progression.…”

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confidence: 85%

Prostate cancer cells modulate osteoblast mineralisation and osteoclast differentiation through Id-1

Chan

et al. 2009

Br J Cancer

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BACKGROUND: Id-1 is overexpressed in and correlated with metastatic potential of prostate cancer. The role of Id-1 in this metastatic process was further analysed. METHODS: Conditioned media from prostate cancer cells, expressing various levels of Id-1, were used to stimulate pre-osteoclast differentiation and osteoblast mineralisation. Downstream effectors of Id-1 were identified. Expressions of Id-1 and its downstream effectors in prostate cancers were studied using immunohistochemistry in a prostate cancer patient cohort (N ¼ 110). RESULTS: We found that conditioned media from LNCaP prostate cancer cells overexpressing Id-1 had a higher ability to drive osteoclast differentiation and a lower ability to stimulate osteoblast mineralisation than control, whereas conditioned media from PC3 prostate cancer cells with Id-1 knockdown were less able to stimulate osteoclast differentiation. Id-1 was found to negatively regulate TNF-b and this correlation was confirmed in human prostate cancer specimens (P ¼ 0.03). Furthermore, addition of recombinant TNF-b to LNCaP Id-1 cell-derived media blocked the effect of Id-1 overexpression on osteoblast mineralisation. CONCLUSION: In prostate cancer cells, the ability of Id-1 to modulate bone cell differentiation favouring metastatic bone disease is partially mediated by TNF-b, and Id-1 could be a potential therapeutic target for prostate cancer to bone metastasis.

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Id-1 and Id-2 Proteins as Molecular Markers for Human Prostate Cancer Progression

Cited by 101 publications

References 27 publications

Id-1 and Id-2 are markers for metastasis and prognosis in oesophageal squamous cell carcinoma

Id-1 and Id-2 are markers for metastasis and prognosis in oesophageal squamous cell carcinoma

Reassessment of Id1 Protein Expression in Human Mammary, Prostate, and Bladder Cancers Using a Monospecific Rabbit Monoclonal Anti-Id1 Antibody

Prostate cancer cells modulate osteoblast mineralisation and osteoclast differentiation through Id-1

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