論文 - 詳細
RRC ID | 17617 |
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著者 | Takahashi Y, Iwai M, Kawai T, Arakawa A, Ito T, Sakurai-Yageta M, Ito A, Goto A, Saito M, Kasumi F, Murakami Y. |
タイトル | Aberrant expression of tumor suppressors CADM1 and 4.1B in invasive lesions of primary breast cancer. |
ジャーナル | 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. |
巻・号 | 19(3) |
ページ | 242-52 |
公開日 | 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 |
引用数 | 56 |
WOS 分野 | OBSTETRICS & GYNECOLOGY ONCOLOGY |
リソース情報 | |
ヒト・動物細胞 | MDA-MB-453(RCB1192) |