Downregulation of TSLC1 and DAL-1 expression occurs frequently in breast cancer

Abstract

TSLC1 and DAL-1 are tumor suppressor genes involved in cell adhesion. In this study, we examined the expression and methylation pattern of these genes in breast cancer cell lines and primary breast carcinomas. TSLC1 expression was lost in 5 of 8 (63%) and DAL-1 expression was lost in 6 of 8 (75%) breast cancer cell lines, respectively. Downregulation of TSLC1 expression was observed in 43 of 50 (86%) and of DAL-1 expression in 26 of 55 (47%) primary breast carcinomas. TSLC1 methylation was found in 4 of 8 (50%) and DAL-1 methylation was observed in 6 of 8 (75%) breast cancer cell lines, respectively. Of 95 primary breast carcinomas 46 (48%) were TSLC1 methylated and 26 (27%) were DAL-1 methylated. Twenty of 43 (47%) and 10 of 26 (38%) primary breast cancer samples which showed downregulation of TSLC1 and DAL-1 expression were unmethylated for these genes. Re-expression of TSLC1 and DAL-1 was observed after treatment of BT-20 cells with 5-aza-2'-deoxycytidine and TSA. Samples from patients with grade 3 tumors were more frequently TSLC1 and TSLC1 and/or DAL-1 methylated than samples from patients with grade 1 and 2 tumors (P = 0.032, P = 0.023). Moreover, TSLC1 methylation correlated with loss of both ER and PgR staining (P = 0.011, P = 0.02). Our findings suggest that TSLC1 and DAL-1 are involved in the pathogenesis of breast cancer and are frequently inactivated by methylation.

Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell survival in neuroblastoma

“…The putative tumour suppressor gene CADM1 has been described to be inactivated in numerous solid human tumours including liver, pancreatic, breast, brain and prostate cancers (Kuramochi et al, 2001;Fukuhara et al, 2002;Jansen et al, 2002;Houshmandi et al, 2006;Heller et al, 2007), and there has been considerable interest in understanding the biological significance of CADM1 loss in tumourigenesis. Previous investigations have supported the hypothesis of CADM1 as a general tumour suppressor-mediating apoptosis (Mao et al, 2004), differentiation (Wakayama et al, 2003) and cell cycle regulation (Ito et al, 2003b).…”

“…This gene maps to chromosome 11q23.2, a region frequently deleted in tumours such as malignant melanoma (Katoh, 2003(Katoh, , 2004, lung cancer (Gomyo et al, 1999) and neuroblastoma (Mertens et al, 1997), and encodes an immunoglobulin superfamily transmembrane molecule primarily involved in epithelial cell adhesion (Murakami, 2005). Loss of CADM1 expression has been described in many malignancies, including liver, pancreatic, breast, brain and prostate cancers, particularly in those showing invasion or metastasis (Kuramochi et al, 2001;Fukuhara et al, 2002;Jansen et al, 2002;Houshmandi et al, 2006;Heller et al, 2007). Promoter hypermethylation was reported to account for downregulation of CADM1 in several human cancers (Murakami, 2005;Ehrlich et al, 2006;Kikuchi et al, 2006;Worsham et al, 2006).…”

Methylation of viral and host genes and severity of cervical lesions associated with human papillomavirus type 16

“…DAL-1 belongs to the protein 4.1 family of molecules and binds actin filaments, functioning as a cytoskeletal regulator; it is classified as a tumour suppressor gene with involvement in cell motility, invasion and progression. 20,21,24,25 The human LMX1A gene, located in chromosome 1, encodes a transcription factor that is involved in developmental processes. 26 Methylation was measured in the viral HPV16 L1 sites 6367 and 6389; and the host genes EPB41L3 (CpG sites 438, 427 and 425) and LMX1A (CpG sites 260, 262, 266 and 274).…”

Atypical 11q deletions identified by array CGH may be missed by FISH panels for prognostic markers in chronic lymphocytic leukemia

“…Deregulation of the TSLC1 tumor suppressor gene has been described in a number of human malignancies, including neuroblastoma, nasopharyngeal carcinoma, breast cancer, lung adenocarcinoma, high-grade gliomas, pancreatic adenocarcinoma, esophageal squamous cell carcinoma, some forms of primary gastric cancer and prostate cancer. [23][24][25][26][27][28][29][30][31][32] The altered expression of TSLC1 has been associated with both promoter hypermethylation, as well as loss of heterozygosity. 25,29,[30][31][32] Each of these three putative deletion target genes is located clearly within the minimally deleted region on 11q as determined by both BAC and oligonucleotide array CGH, in all four of the CLL cases with atypical 11q deletions included in this study.…”