Increased Expression of Id Family Proteins in Small Cell Lung Cancer and its Prognostic Significance

Abstract

Purpose: To study the molecular pathology of human small cell lung cancer (SCLC), molecular biology approaches were used to identify genes involved in malignant progression of the cancer cells. Experimental Design: Microquantity differential display was used initially to identify genes expressed differentially between normal and malignant cell lines. The differences were verified by Western blot. Immunohistochemical analysis was done on paired normal and malignant lung tissues and on tissues taken by biopsy to assess the expression status of candidate genes and their prognostic significance. Results: Inhibitor of DNA/differentiation (Id)1 gene was up-regulated in SCLC cells. Levels of Id1in 8 of 10 cell lines were increased by 1.7-to 21.4-fold when compared with the benign cells. A similar increase was also found in levels of Id2 and Id3. On 26 pairs of lung tissues, all four Id proteins were significantly (Wilcoxon Signed Rank Test, P < 0.001-0.005) overexpressed in cytoplasm of the malignant cells. In nuclei of SCLC cells, Id1 expression was significantly reduced, whereas the levels of Id2, Id3, and Id4 were significantly (Wilcoxon Signed Rank Test, P < 0.001) increased. Immunohistochemical staining on biopsy specimens showed that the increased expression of Id2 in cytoplasm of cancer cells, not the other three proteins, was significantly associated with the increased survival of SCLC patients. Conclusion: Changed expression profiles of Id proteins may play important roles in malignant progression of SCLC, and the increased Id2 in cytoplasm is a novel prognostic factor to predict the patient outcomes.

Atelocollagen-delivered siRNA targeting the FABP5 gene as an experimental therapy for prostate cancer in mouse xenografts

“…The other was fixed in neutral-buffered formaldehyde (10% w/v) and embedded in paraffin wax. From these, histological sections (4 μm) were cut and mounted onto APES slides using standard routine procedures (17,18). Tissue sections were stained with haematoxylin and eosin to assess tumour morphology.…”

Inhibition of tumourigenicity of small cell lung cancer cells by suppressing Id3 expression

“…This indicated that Id proteins may play important roles in the pathogenesis of malignant progression and that they may be new potential targets for tumour suppression (1). This study has focused on Id3 protein, which showed the most pronounced over-expression amongst the Id-family proteins in SCLC, to test whether reduced expression of this protein can suppress the tumourigenicity of SCLC cells in vitro and in vivo.…”

“…Despite all efforts in understanding the molecular biology of this tumour, the underlying genetic alteration responsible for its unique disseminative behaviour is not clear. Previously, we showed that inhibitors of differentiation/ DNA binding (Id) family proteins were generally overexpressed in malignant SCLC cell lines and tissue samples when compared to their normal bronchial epithelial counterparts and suggested that they might be involved in carcinogenesis and progression of SCLC (1). Amongst the Id family proteins overexpressed in SCLC, Id3 exhibited the most pronounced change in its expression level.…”

“…Also, Id2 and Id3 were over-expressed in T cell leukemia (26). More recently, the increased expression in SCLC and its possible prognostic significance were investigated and the increased Id2 in cytoplasm was found to be significantly related to increased survival of patients (1).…”

“…GLC-19 cells were shown to express the highest level of the Id3 protein amongst the 10 SCLC cell lines tested previously (1). The Id3-suppressed cells derived from GLC-19 were subjected to a series of bioassays in vitro and in vivo to test the effect of reducing Id3 expression on the malignant characteristics of the cells.…”