美国哥伦比亚大学医学中心等机构的研究人员9月9日报告说，他们在成年实验鼠前列腺中发现的干细胞可能是一种前列腺癌干细胞。
研究人员说，这种被命名为“CARN”的干细胞在实验鼠前列腺组织再生过程中发挥作用，如果某些肿瘤抑制基因未能开启，这种干细胞就可以造成前列腺癌变。
研究人员还发现，这种干细胞并不依赖实验鼠的雄性激素存活和生长，这或许可以解释为何一些晚期前列腺癌患者对旨在调控雄性激素的疗法产生抵抗。
这项研究成果9日发表在英国《自然》杂志网络版上。研究人员说，尽管这只是一项动物实验，但弄清前列腺中哪些细胞引发癌症有助于开发出更好的前列腺癌疗法。
癌干细胞又称肿瘤干细胞，它们在肿瘤中具有自我更新能力并能产生异质性癌细胞，因具有干细胞的特性而得名。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature advance online publication 9 September 2009 | doi:10.1038/nature08361
A luminal epithelial stem cell that is a cell of origin for prostate cancer
Xi Wang1,2,5,6, Marianna Kruithof-de Julio1,2, Kyriakos D. Economides5,7,8, David Walker5,6,8, Hailong Yu5,6,8, M. Vivienne Halili5,6,8, Ya-Ping Hu5,6,8, Sandy M. Price5,6, Cory Abate-Shen3,4,5,7 & Michael M. Shen1,2,5,6
1 Department of Medicine,
2 Department of Genetics and Development,
3 Department of Urology, and,
4 Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
5 Center for Advanced Biotechnology and Medicine,
6 Department of Pediatrics, and,
7 Department of Medicine, UMDNJ–Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
8 Present addresses: Department of Biological Sciences, Sanofi-Aventis, Bridgewater, New Jersey 08807, USA (K.D.E.); Department of Molecular Biology, Bristol-Myers Squibb Research Institute, Princeton, New Jersey 08543, USA (D.W.); Department of Food Science, Rutgers University, Piscataway, New Jersey 08901, USA (H.Y.); Cardiovascular Diseases Group, Merck Research Laboratories, Rahway, New Jersey 07065, USA (M.V.H.); Johnson and Johnson Skin Research Center, Skillman, New Jersey 08558, USA (Y.-P.H.); Department of Medical Oncology, Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA (S.M.P.).
9 Correspondence to: Michael M. Shen1,2,5,6 Correspondence and requests for materials should be addressed to M.M.S.
In epithelial tissues, the lineage relationship between normal progenitor cells and cell type(s) of origin for cancer has been poorly understood. Here we show that a known regulator of prostate epithelial differentiation, the homeobox gene Nkx3-1, marks a stem cell population that functions during prostate regeneration. Genetic lineage-marking demonstrates that rare luminal cells that express Nkx3-1 in the absence of testicular androgens (castration-resistant Nkx3-1-expressing cells, CARNs) are bipotential and can self-renew in vivo, and single-cell transplantation assays show that CARNs can reconstitute prostate ducts in renal grafts. Functional assays of Nkx3-1 mutant mice in serial prostate regeneration suggest that Nkx3-1 is required for stem cell maintenance. Furthermore, targeted deletion of the Pten tumour suppressor gene in CARNs results in rapid carcinoma formation after androgen-mediated regeneration. These observations indicate that CARNs represent a new luminal stem cell population that is an efficient target for oncogenic transformation in prostate cancer.
