TY - JOUR
T1 - Downregulation of TSLC1 and DAL-1 expression occurs frequently in breast cancer
AU - Heller, Gerwin
AU - Geradts, Joseph
AU - Ziegler, Barbara
AU - Newsham, Irene
AU - Filipits, Martin
AU - Markis-Ritzinger, Eva Maria
AU - Kandioler, Daniela
AU - Berger, Walter
AU - Stiglbauer, Wolfgang
AU - Depisch, Dieter
AU - Pirker, Robert
AU - Zielinski, Christoph C.
AU - Zöchbauer-Müller, Sabine
N1 - Funding Information:
(GZ 200.062/2-VI/1/2002), by the Medical-Scientific Fund of the Mayor of the Federal Capital Vienna, by an award from the ‘‘Fonds der Stadt Wien für Innovative Interdisziplinäre Krebs-forschung’’ and by the Ludwig Boltzmann Institute for Clinical and Experimental Oncology.
Funding Information:
Acknowledgments This study was supported by grants from the Austrian Federal Ministry of Education, Science and Culture
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
KW - Breast cancer
KW - DAL-1
KW - Methylation
KW - TSLC1
KW - Tumor suppressor gene
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U2 - 10.1007/s10549-006-9377-7
DO - 10.1007/s10549-006-9377-7
M3 - Article
C2 - 17260099
AN - SCOPUS:34249313493
SN - 0167-6806
VL - 103
SP - 283
EP - 291
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -