The expression of SIAH1 is downregulated and associated with Bim and apoptosis in human breast cancer tissues and cells.
Seven in absentia homolog1 (SIAH1) was reported as a tumor suppressor and played an important role in regulating cell apoptosis. However, its effects on the breast carcinogenesis remain unclear. In this study, our aims were to examine the relationship between SIAH1 and Bcl-2-interacting mediator of cell death (Bim) and to explore the effects of SIAH1 on the breast carcinogenesis. Immunohistochemical analysis in 231 cases of breast tissues showed that the expression of SIAH1 and Bim were significantly decreased in the breast carcinogenesis. Moreover, SIAH1 expression was significantly correlated with Bim. Both SIAH1 and Bim expression were significantly higher in well to moderately differentiated and in early-stage breast cancer. Reverse transcription (RT)-polymerase chain reaction (PCR) and Western blot analysis in paired breast cancer tissues and breast cell lines found that the expression of SIAH1 was lower in the breast cancer tissues and cell lines. SIAH1 inducing apoptosis of the breast cancer cells was dependent on Bim. However, SIAH1 inhibiting invasion of the breast cancer cells was independent of Bim. The increase of the function of SIAH1 to upregulate the expression of Bim may play an important role in the progression of breast cancer. Restoration of the function of SIAH1 may be a new therapeutic target of human breast cancer.
Wen
Yuan-Yuan
YY
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Heping District, Shenyang, China.
Yang
Zhi-Qiang
ZQ
Song
Min
M
Li
Bai-Lin
BL
Yao
Xiao-Hui
XH
Chen
Xiao-Ling
XL
Zhao
Jing
J
Lu
Yi-Yan
YY
Zhu
Ji-Jiang
JJ
Wang
En-Hua
EH
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001483:Base Sequence; D000072224:Bcl-2-Like Protein 11; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D017931:DNA Primers; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism* / Q000502:physiology; D000098563:Seven in Absentia Proteins
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D017931:DNA Primers; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins