德國研究人員1日說,，他們鑒定出115種與結(jié)腸癌轉(zhuǎn)移相關(guān)的基因,，這項成果將有望幫助早期診斷結(jié)腸癌患者的腫瘤是否有擴散危險,。
癌細胞轉(zhuǎn)移是導致結(jié)腸癌患者死亡的重要原因,。為調(diào)查哪些基因促進癌細胞轉(zhuǎn)移,，德國馬克斯·德爾布呂克分子醫(yī)學中心和柏林沙里泰大學醫(yī)院的研究人員分析了150份癌細胞轉(zhuǎn)移和未轉(zhuǎn)移的結(jié)腸癌患者的組織樣本,，結(jié)果鑒定出115個在原發(fā)病灶和轉(zhuǎn)移癌細胞中都有的基因,，由此找出了區(qū)別轉(zhuǎn)移性腫瘤和非轉(zhuǎn)移性腫瘤的基因標志。
研究人員進而又研究了其中一種名為“BAMBI”的基因,。結(jié)果發(fā)現(xiàn),，這種基因在轉(zhuǎn)移性腫瘤和轉(zhuǎn)移癌細胞中比在非轉(zhuǎn)移性腫瘤中更活躍。研究還顯示,，這種基因與Wnt－β和TGF－β兩種重要的傳導通路有關(guān),，從而促使癌細胞轉(zhuǎn)移。
研究人員說,，他們將繼續(xù)研究另外114種基因,，以更好地了解癌細胞轉(zhuǎn)移的具體原因。（生物谷Bioon.com）
生物谷推薦原始出處：
Gastroenterology July 2009,doi:10.1053/j.gastro.2009.03.041
A Colorectal Cancer Expression Profile That Includes Transforming Growth Factor β Inhibitor BAMBI Predicts Metastatic Potential
Johannes Fritzmann, ?, Markus Morkel, Daniel Besser, Jan Budczies§, Frauke Kosel, Felix H. Brembeck, Ulrike Stein, ?, Iduna Fichtner, Peter M. Schlag, ? and Walter Birchmeier, ,
Department for Surgery and Surgical Oncology, Berlin, Germany
Max Delbrueck Center for Molecular Medicine, Berlin, Germany
Institute for Pathology, Charité-University Medical School, Berlin, Germany
Background & Aims
Much is known about the genes and mutations that cause colorectal cancer (CRC), yet only a few have been associated with CRC metastasis. We performed expression-profiling experiments to identify genetic markers of risk and to elucidate the molecular mechanisms of CRC metastasis.
Methods
We compared gene expression patterns between metastatic and nonmetastatic stage-matched human colorectal carcinomas by microarray analysis. Correlations between BAMBI and metastasis-free survival were examined by quantitative real-time polymerase chain reaction (PCR) using an independent set of human colon carcinomas. Human colon cancer cell lines were analyzed for BAMBI regulation, cell motility, and experimental metastasis.
Results
We established a signature of 115 genes that differentiated metastatic from nonmetastatic primary tumors. Among these, the transforming growth factor (TGF) β inhibitor BAMBI was highly expressed in approximately half of metastatic primary tumors and metastases but not in nonmetastatic tumors. BAMBI is a target of canonical Wnt signaling that involves the β-catenin coactivator BCL9-2. We observed an inverse correlation between level of BAMBI expression and metastasis-free survival time of patients. BAMBI inhibits TGF-β signaling and increases migration in colon cancer cells. In mice, overexpression of BAMBI caused colon cancer cells to form tumors that metastasized more frequently to liver and lymph nodes than control cancer cells.
Conclusions
BAMBI regulates CRC metastasis by connecting the Wnt/β-catenin and TGF-β-signaling pathways. The metastatic expression signature we describe, along with BAMBI levels, can be used in prognosis. Developmental signaling pathways appear to act in hierarchies and cooperate in tumor cell migration, invasion, and metastasis.
