Downregulation of TSLC1 and DAL-1 expression occurs frequently in breast cancer.
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.
Heller
Gerwin
G
Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Geradts
Joseph
J
Ziegler
Barbara
B
Newsham
Irene
I
Filipits
Martin
M
Markis-Ritzinger
Eva-Maria
EM
Kandioler
Daniela
D
Berger
Walter
W
Stiglbauer
Wolfgang
W
Depisch
Dieter
D
Pirker
Robert
R
Zielinski
Christoph C
CC
Zöchbauer-Müller
Sabine
S
D001374:Azacitidine / Q000031:analogs & derivatives / Q000737:chemistry; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D002448:Cell Adhesion; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D045744:Cell Line, Tumor; D019175:DNA Methylation; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000235:genetics*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D008840:Microfilament Proteins; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013447:Sulfites / Q000737:chemistry; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics*
C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; C116887:EPB41L3 protein, human; D007136:Immunoglobulins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D013447:Sulfites; D025521:Tumor Suppressor Proteins; D012313:RNA; D000077209:Decitabine; D001374:Azacitidine; C042345:hydrogen sulfite