The role and the potential regulatory pathways of high expression of forkhead box C1 in promoting tumor growth and metastasis of basal-like breast cancer.
OBJECTIVE
To investigate the role of high forkhead box C1 (FOXC1) expression in basal-like breast cancer (BLBC) in vitro and vivo and the underlying regulatory mechanism.


METHODS
The lentivirus vector with green fluorescent protein (GFP) was used. MDA-MB-231 cells expressing consistently high levels of FOXC1 (FOXC1-MDA-MB-231) were established. The parental MDA-MB-231 cells served as controls. Western blot analysis was used to determine the FOXC1 expression. The invasion capability was tested using the Trans-well assay. The tumorigenicity and the pulmonary metastatic ability were determined in mice in vivo. Histopathology and microarray processing and analysis were performed, and the various pathways involved and the related genes were analyzed.


RESULTS
The invasion ability of FOXC1-MDA-MB-231 cells was enhanced significantly (p<0.01). Pulmonary metastases were observed in vivo in 3 of 5 mice administered FOXC1-MDA-MB-231 cells through tail vein injection. However, no pulmonary metastatic lesions were observed with MDA-MB-231 cells. The average tumor volume was larger in the mice injected with FOXC1-MDA-MB-231 than in the control mice (p<0.05). The expression of Ki-67 in the FOXC1-MDA-MB-231 injected mice was higher than in the control mice. Ten of the most gene-enriched pathways and the critical genes (IL-6 and SNAI2) were found to be related to BLBC.


CONCLUSIONS
Elevated expression of FOXC1 enhanced the invasion ability of BLCB cells in vitro and promoted tumor growth and metastatic ability in vivo. This function may be regulated by many gene-enriched pathways and some critical genes.
Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China;
Hou Dong
HD
Zuo
Wei
W
Wu Yao
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D019394:Ki-67 Antigen / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D047368:Tumor Burden / Q000235:genetics
C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D015850:Interleukin-6; D019394:Ki-67 Antigen