Down regulation of fibulin-1 in squamous cell carcinoma of the oesophagus

Abstract

The molecular events involved in the development of squamous cell oesophageal cancer remain poorly understood. To elucidate the probable genetic events involved, genes that are differentially expressed between normal and tumour oesophageal tissue were identified. Differential display reverse transcription polymerase chain reaction was carried out on both malignant and adjacent normal oesophageal tissue of the same patient to identify differentially expressed genes in oesophageal cancer patients. Differentially expressed genes were isolated, cloned, sequenced and identified in GenBank using BLAST. Fibulin-1 was identified as one of the differentially expressed genes. Northern blot analysis confirmed down regulation of fibulin-1 in oesophageal cancer tissues, while immunohisto-chemical studies using a larger patient sample localized fibulin-1 to both the cell membrane and cytoplasm of both cancer cells and corresponding normal epithelial tissue. Whereas the protein was abundant in the normal oesophageal epithelial cells, its expression was significantly reduced in dysplastic cells and in the different grades of oesophageal cancer cells. This observation suggests that fibulin-1 down regulation in oesophageal cancer is an early event and is probably influenced by the grade of the tumour. This is the first study to report on the relationship between fibulin-1 expression and oesophageal cancer tumour grade. It forms the basis for further evaluation of this gene as a candidate biomarker in cancer of the oesophagus and its probable role in the early events of tumourigenesis. Key words: Oesophageal cancer, fibulin, differential display, tumour markers.