Evidence for a Tumour Suppressor Function of SETD2 in Human Breast Cancer: A New Hypothesis

• Published in: Anticancer research Vol. 30; no. 9; pp. 3309 - 3311
• Main Authors: NEWBOLD, R. F, MOKBEL, K
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.09.2010
• Subjects: Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Female; Gene Expression; Gene Expression Profiling; Genes, Tumor Suppressor; Gynecology. Andrology. Obstetrics; Histone-Lysine N-Methyltransferase - biosynthesis; Histone-Lysine N-Methyltransferase - genetics; Humans; Immunohistochemistry; Mammary gland diseases; Medical sciences; Reverse Transcriptase Polymerase Chain Reaction; Tumors; Human; SETD2; Breast disease; Enzyme; Transferases; Breast cancer; Malignant tumor; Mammary gland diseases; Cancerology; histone methyltransferase; Methyltransferases; Histone; Telomerase; Cancer; Tumor suppressor gene
• ISSN: 0250-7005; 1791-7530

SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. We previously demonstrated SETD2 to be a potential tumour suppressor gene in breast cancer. The aim of this study was to compare SETD2 expression in breast cancer with that in adjacent non-cancerous breast tissue (ANCT) in paired samples. A hypothesis is proposed that explains the mode of action of SETD2 as a tumour suppressor gene. Paired samples of tumour and adjacent non-cancerous tissue (ANCT) from 25 patients were analysed. The levels of transcription of SETD2 were determined using quantitative polymerase chain reaction and normalized against cytokeratin 19. Immunohistochemical staining with appropriate antibodies against SETD2 protein was also performed in selected samples. Levels of SETD2 mRNA were significantly higher in ANCT when compared to those in tumour samples (p=0.01). Immunohistochemistry also demonstrated a higher protein expression in ANCT. This study offers further evidence that SETD2 behaves like a tumour suppressor gene. Our hypothesis links SETD2 mode of action with telomerase regulation through human telomerase reverse transcriptase (hTERT). Several studies have emphasised the importance of histone methylation of hTERT promotor in telomerase regulation. SETD2 function of histone methylation could be the missing link in this chain which could explain the potential tumour suppressor function of SETD2.