Differential role of MACC1 expression and its regulation of the HGF/c‑Met pathway between breast and colorectal cancer.
The newly identified gene, metastasis‑associated in colon cancer 1 (MACC1), is suggested to be a transcriptional regulator of c‑Met, leading to cancer progression in colorectal cancer. To date however, little is known of the role of MACC1 in breast cancer. In a series of 300 breast cancer patients, we analyzed the association of MACC1 mRNA and protein expression with breast cancer survival using Cox proportional hazard models. In an in vitro study, we evaluated activities of c‑Met protein after transfection with a MACC1‑harboring plasmid as well as the binding ability of MACC1 to the c‑Met promoter using a chromatin immunoprecipitation (ChIP) assay. In survival analyses, reduced MACC1 expression was associated with patient mortality. MACC1 expression was an independent prognostic factor in multivariate analysis. In the cell lines tested, MACC1 expression was much higher in colorectal than in breast cancer cells. After cells were transfected with MACC1, c‑Met expression was not induced in MCF7 cells, whereas corresponding c‑Met expression was upregulated in SW480 cells. Further, SW480 cells transfected with MACC1 showed enhanced migratory ability, whereas in MDA‑MB‑231 cells, transfection of MACC1 had no impact on this ability. In ChIP assay, the binding of MACC1 to the c‑Met promoter was suggested in SW480 cells, but not in MCF7 cells. In conclusion, our findings provide some novel insights into the role of MACC1 in breast cancer, indicating that it plays different roles in breast and several other cancers. There is a possibility that MACC1 does not modulate the transcriptional role of c‑Met signaling in breast cancer.
Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860‑8556, Japan.
Aiko
A
Sueta
Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860‑8556, Japan.
Yutaka
Y
Yamamoto
Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860‑8556, Japan.
Mutsuko
M
Yamamoto-Ibusuki
Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860‑8556, Japan.
Mitsuhiro
M
Hayashi
Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860‑8556, Japan.
Takashi
T
Takeshita
Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860‑8556, Japan.
Satoko
S
Yamamoto
Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860‑8556, Japan.
Yoko
Y
Omoto
Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860‑8556, Japan.
Hirotaka
H
Iwase
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016016:Proportional Hazards Models; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection
C066855:HGF protein, human; C544162:MACC1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met