每一天，你身体内的一些细胞会停止分裂，这是一件好事。而有些细胞会无限增殖，这是大多数恶性肿瘤发展的一个重要早期步骤。

尽管细胞无限增殖在癌症中有着非常的重要性，但研究人员一直对于细胞永生化背后的分子机制知之甚少。这是因为科学家缺乏好方法研究永生化人类细胞。在发表在Cell Cycle 杂志上的一项研究中，研究人员已经开发出一种新方法，能够轻松地创建出不朽的人类乳腺上皮细胞。

与大多数人来源的“不朽”细胞(包括从肿瘤组织中获得细胞)不同，这些新创建的不朽细胞具有正常的基因组。伯克利实验室生命科学部科学家Martha Stampfer说：这些细胞可能有助于开辟新的策略来对抗癌症。细胞永生化也可以是一个重要的治疗靶标。

Stampfer补充道：现在我们可以获得携带正常基因组的无限增殖的人类乳腺上皮细胞，去探索细胞永生化的背后分子机制，我们也可以开始思考如何针对细胞永生化这一过程，防止或逆转癌症的发展。

原文摘要：

Immortalization of normal human mammary epithelial cells in two steps by direct targeting of senescence barriers does not require gross genomic alterations

Hiroyasu Yamamoto, Evan G. Williams, Laurent Mouchiroud, Carles Cantó, Weiwei Fan, Michael Downes, Christophe Héligon, Grant D. Barish, BéatrICE Desvergne, Ronald M. Evans et al.

Telomerase reactivation and immortalization are critical for human carcinoma progression. However, little is known about the mechanisms controlling this crucial step, due in part to the paucity of experimentally tractable model systems that can examine human epithelial cell immortalization as it might occur in vivo. We achieved efficient non-clonal immortalization of normal human mammary epithelial cells (HMEC) by directly targeting the 2 main senescence barriers encountered by cultured HMEC. The stress-associated stasis barrier was bypassed using shRNA to p16INK4; replicative senescence due to critically shortened telomeres was bypassed in post-stasis HMEC by c-MYC transduction. Thus, 2 pathologically relevant oncogenic agents are sufficient to immortally transform normal HMEC. The resultant non-clonal immortalized lines exhibited normal karyotypes. Most human carcinomas contain genomically unstable cells, with widespread instability first observed in vivo in pre-malignant stages; in vitro, instability is seen as finite cells with critically shortened telomeres approach replicative senescence. Our results support our hypotheses that: (1) telomere-dysfunction induced genomic instability in pre-malignant finite cells may generate the errors required for telomerase reactivation and immortalization, as well as many additional “passenger” errors carried forward into resulting carcinomas; (2) genomic instability during cancer progression is needed to generate errors that overcome tumor suppressive barriers, but not required per se; bypassing the senescence barriers by direct targeting eliminated a need for genomic errors to generate immortalization. Achieving efficient HMEC immortalization, in the absence of “passenger” genomic errors, should facilitate examination of telomerase regulation during human carcinoma progression, and exploration of agents that could prevent immortalization.

 干细胞治疗使用的 lonza 12-725F 无血清培养基 （点击标题进入）