RRC ID 17617
Author Takahashi Y, Iwai M, Kawai T, Arakawa A, Ito T, Sakurai-Yageta M, Ito A, Goto A, Saito M, Kasumi F, Murakami Y.
Title Aberrant expression of tumor suppressors CADM1 and 4.1B in invasive lesions of primary breast cancer.
Journal Breast Cancer
Abstract BACKGROUND:The tumor suppressor genes CADM1/TSLC1 and DAL-1/4.1B are frequently inactivated by promoter methylation in non-small cell lung cancer. The proteins they encode, CADM1 and 4.1B, form a complex in human epithelial cells and are involved in cell-cell adhesion.
METHODS:Expression of CADM1 and 4.1B proteins was examined by immunohistochemistry in 67 primary breast cancer and adjacent noncancerous tissues. CADM1 and 4.1B messenger RNA (mRNA) was detected by reverse-transcription polymerase chain reaction (RT-PCR). The methylation status of the CADM1 and 4.1B promoters was determined quantitatively by bisulfite treatment followed by pyrosequencing.
RESULTS:CADM1 and 4.1B protein signals were detected along the cell membrane in normal mammary epithelia. By contrast, 47 (70%) and 49 (73%) of 67 primary breast cancers showed aberrant CADM1 and 4.1B staining, respectively. Aberrant CADM1 staining was more frequently observed in pT2 and pT3 tumors and for stages II and III (P = 0.045 and P = 0.020, respectively), while aberrant 4.1B staining was more often observed in tumors with lymph node metastasis, for pT2 and pT3 tumors, and for stages II and III (P = 0.0058, P = 0.0098, and P = 0.0007, respectively). Furthermore, aberrant CADM1 and 4.1B expression was preferentially observed in invasive relative to noninvasive lesions from the same specimen (P = 0.036 and P = 0.0009, respectively). Finally, hypermethylation of CADM1 and 4.1B genes was detected in 46% and 42% of primary breast cancers, respectively.
CONCLUSIONS:Our findings suggest that aberrant CADM1 and 4.1B expression is involved in progression of breast cancer, especially in invasion into the stroma and metastasis.
Volume 19(3)
Pages 242-52
Published 2012-7-1
DOI 10.1007/s12282-011-0272-7
PMID 21526423
MeSH Adult Aged Aged, 80 and over Breast Neoplasms / genetics* Breast Neoplasms / metabolism Breast Neoplasms / pathology* Cell Adhesion Molecule-1 Cell Adhesion Molecules / genetics* Cell Adhesion Molecules / metabolism Cell Line, Tumor Cell Membrane / metabolism DNA Methylation Epithelial Cells / metabolism Female Gene Expression Regulation, Neoplastic Humans Immunoglobulins / genetics* Immunoglobulins / metabolism Membrane Proteins / genetics* Membrane Proteins / metabolism Middle Aged Neoplasm Invasiveness Neoplasm Staging Promoter Regions, Genetic Reference Values Stromal Cells / pathology Tumor Suppressor Proteins / genetics
IF 2.695
Times Cited 56
Human and Animal Cells MDA-MB-453(RCB1192)