胃腸道組織的細菌感染可能引發(fā)了遺傳易感人群的前癌細胞的發(fā)育,。Laurence Rahme及其同事用一種綠膿桿菌（Pseudomonas aeruginosa）的有毒菌株感染了經(jīng)過遺傳改造的果蠅,，這種細菌也能感染人類,。結果他們發(fā)現(xiàn)了細菌感染與腸道細胞發(fā)育不良之間的聯(lián)系,。這個經(jīng)過改造的果蠅模型含有了Ras基因,，科學家已經(jīng)把這種基因與許多類型的癌癥聯(lián)系了起來,。
這組科學家發(fā)現(xiàn),，這種病原體的感染對于這些具有遺傳易感性的果蠅起到了協(xié)同增效的作用,；它極大地增加了果蠅腸道內(nèi)的新的腸道干細胞的數(shù)量,，而且這些細胞中的許多表現(xiàn)出了不正常的細胞極性，這是癌癥的標記,。在綠膿桿菌從果蠅腸道中清除出去之后,，這些異常細胞仍然存在，這提示感染對于引發(fā)腫瘤具有持久相應,。腸組織能迅速再生,，但是病原體感染和腸自我更新的組合可能導致慢性胃腸病。這組作者說,，這項研究可能有助于抗擊癌癥,，而且可能有助于開發(fā)更好的診斷工具。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS November 23, 2009, doi: 10.1073/pnas.0911797106
Synergy between bacterial infection and genetic predisposition in intestinal dysplasia
Yiorgos Apidianakisa,b,1, Chrysoula Pitsoulic,1, Norbert Perrimonc,2 and Laurence Rahmea,b,d,2
aDepartment of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115;
bShriners Burns Institute, Boston, MA 02114;
cDepartment of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115; and
dDepartment of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115
Accumulating evidence suggests that hyperproliferating intestinal stem cells (SCs) and progenitors drive cancer initiation, maintenance, and metastasis. In addition, chronic inflammation and infection have been increasingly recognized for their roles in cancer. Nevertheless, the mechanisms by which bacterial infections can initiate SC-mediated tumorigenesis remain elusive. Using a Drosophila model of gut pathogenesis, we show that intestinal infection with Pseudomonas aeruginosa, a human opportunistic bacterial pathogen, activates the c-Jun N-terminal kinase (JNK) pathway, a hallmark of the host stress response. This, in turn, causes apoptosis of enterocytes, the largest class of differentiated intestinal cells, and promotes a dramatic proliferation of SCs and progenitors that serves as a homeostatic compensatory mechanism to replenish the apoptotic enterocytes. However, we find that this homeostatic mechanism can lead to massive over-proliferation of intestinal cells when infection occurs in animals with a latent oncogenic form of the Ras1 oncogene. The affected intestines develop excess layers of cells with altered apicobasal polarity reminiscent of dysplasia, suggesting that infection can directly synergize with the genetic background in predisposed individuals to initiate SC-mediated tumorigenesis. Our results provide a framework for the study of intestinal bacterial infections and their effects on undifferentiated and mature enteric epithelial cells in the initial stages of intestinal cancer. Assessment of progenitor cell responses to pathogenic intestinal bacteria could provide a measure of predisposition for apoptotic enterocyte-assisted intestinal dysplasias in humans.
