Epidermal growth factor receptor (EGFR) is suggested as one of the positive regulators in the invasive progression of renal cell cancer (RCC). Recently, Id-1 (inhibitor of differentiation or DNA binding), a helix-loop-helix transcription factor, has been identified as one of the key factors in the EGFR signalling pathway. The aim of this study was to investigate the significance of Id-1 expression in renal cell cancer and to study its relationship with EGFR.
Id-1 and EGFR expression was examined in tissue microarray (TMA) samples of 107 RCC and 32 normal kidney specimens by immunohistochemistry. Relative Id-1 and EGFR protein expression was quantified by estimating the staining intensity on a four-grade scale. We found that while negative to weak expression of Id-1 and EGFR was observed in non-malignant kidney tissues, most RCCs showed significant positive Id-1 and EGFR expression in tumour cells. In addition, Id-1 immunostaining intensity was positively associated with increased tumour staging, grading and EGFR expression.
Overexpression of Id-1 is a novel marker for advanced RCC which is positively correlated with EGFR expression. Our results suggest that Id-1 may play an important role in the development of RCC and indicate that Id-1 is a potential marker of patients with a poor prognosis.
"These studies suggest that ID1 may play a role in the neoplastic transformation of cells. In support of this, ID1 levels have been found to be elevated in a variety of cancers, including breast (Lin et al. 2000; Fong et al. 2003), thyroid (Kebebew et al. 2000), endometrial (Takai et al. 2001), cervical (Schindl et al. 2001), ovarian (Schindl et al. 2003), renal cell (Li et al. 2007), and prostate cancers (Ouyang et al. 2002), and the elevated ID1 levels are correlated with the severity of malignancy (Lin et al. 2000; Ouyang et al. 2001,2002; Fong et al. 2003; Schindl et al. 2003; Li et al. 2007). Although normal prostate and benign prostatic hyperplasia exhibit only very weak levels of ID1, poorly differentiated prostate adenocarcinomas show dramatically increased levels of this protein (Ouyang et al. 2001,2002). "
[Show abstract][Hide abstract] ABSTRACT: Inhibitor of DNA-binding-1 (ID1) negatively regulates cell differentiation and senescence, and enhances cellular proliferation and angiogenesis. Elevated levels of ID1 have been found in a variety of cancers, including prostate cancer, but whether ID1 has a tumourigenic role remains to be established. We established heterozygous and homozygous ID1-transgenic mouse lines driven by the prostate-specific probasin promoter (-426 to +28 bp). Although elevated levels of ID1 were confirmed by RT-PCR, immunohistochemistry, and Western blot analysis, there were no morphological changes identified in the prostate of transgenic mice at 26 and 52 weeks. Thus, overexpression of ID1 alone is not sufficient to drive neoplastic change in mouse prostate.
Journal of Histochemistry and Cytochemistry 04/2009; 57(6):599-604. DOI:10.1369/jhc.2009.953182 · 1.96 Impact Factor
"Recently, it has been proposed that Id-1 is a regulator in the EGFR and VEGF pathway [28-30]. Id-1 mediated cancer cell growth has been shown to be associated with EGFR activation in ovarian and prostate cells [19,24]. "
[Show abstract][Hide abstract] ABSTRACT: The helix-loop-helix transcription factor Id-1 (an inhibitor of differentiation and DNA binding) plays a role in development and progression of many tumours. Id-1 is known to exert its effects on the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF). The aim of this study was to reveal whether there was a relationship between Id-1 and EGFR and VEGF in colorectal carcinoma.
Tumour and non-tumour tissue specimens from 46 cases of colorectal carcinoma were exposed to immunohistochemical staining for Id-1, EGFR and VEGF. The relationship between the degree of staining and tumour grade, tumour stage and all tumour markers was investigated.
Tumour cells showed positive staining for Id-1 in 43 cases (93.5%), for EGFR in 41 cases (89%) and for VEGF in 42 cases (91%). There was a significant relation between the tumour grade and the degree of staining for Id-1, EGFR and VEGF. The relation between the tumour stage and the degree of staining for Id-1, EGFR and VEGF was also significant. There was a significant relation between Id-1 expression and EGFR and VEGF expressions. Non-tumoural tissue specimens were not stained with Id-1 and EGFR antibodies in any of the cases, but stained with VEGF antibody in 3 cases.
This study revealed that Id-1, EGFR and VEGF took part in development and progression of colorectal carcinomas and that Id-1 was associated with regulations of EGFR and VEGF. The results of this study support the idea that not only EGFR and VEGF but also Id-1 could be new targets in cancer treatment.
Journal of Experimental & Clinical Cancer Research 12/2008; 27(1):69. DOI:10.1186/1756-9966-27-69 · 4.43 Impact Factor
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