重编程癌细胞之王：将胰腺癌转变为正常细胞 - 新闻区干细胞之家



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发表于 2015-4-22 11:16 |只看该作者 |倒序浏览 |打印

本帖最后由 sunsong7 于 2015-4-22 13:10 编辑 + G1 g1 ~. x/ n; L& V

胰腺癌突破性进展：将癌细胞转变为正常细胞

http://www.pharmacy.hc360.com2015年04月22日09:20 来源：生物谷T|T( a7 `) U! {9 N3 }! y! O

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一项新的研究发现，胰腺癌细胞可以通过过表达一个名为E47的蛋白，从而被诱导转变回正常的细胞。E47可以与特定的DNA序列结合，来控制掌管生长和分化的一些基因。这项研究为美国每年超过4万死于胰腺癌的患者们提供了拥有新治疗方法的希望。

"这是第一次，我们发现过表达一个基因，就可以降低胰腺腺癌细胞促进肿瘤发展的潜在性，通过将这些癌症细胞重新编程回它们原始的细胞类型。因此，胰腺细胞保留有基因记忆，我们希望可以开发利用。"Sanford-Burnham发育，衰老和再生项目的兼职教授PamelaItkin-Ansari说，她也是这项研究的主要作者。此研究在于4月20日发表在Pancreas杂志上。
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E47将时钟拨了回去, V& [! q5 D6 I: X$ m- O. g

这项研究是几个大学联合合作的成果，包括Sanford-Burnham，圣迭戈大学（Itkin-Ansari负责联合任命）和普渡大学，研究人员们造出了人胰腺导管腺癌细胞系，且E47水平高于正常水平。升高的E47导致了细胞停滞在G0/G1生长期，分化回了腺泡细胞表型。1 I" J- `. s! A5 l

体内实验显示，当这些重新编程的癌症细胞被打入老鼠体内，这些细胞形成肿瘤的能力，与未处理的胰腺癌细胞相比，大大减低。; i+ Q/ O. q/ c- }0 [
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"目前，胰腺腺癌的治疗方法是一些细胞毒性药物，患者在确证后的平均存活时间仅为6个月，治疗的改进时间以天来计算，"圣迭戈大学莫尔斯癌症中心外科教授，美国国家癌症研究所胰腺癌专责小组联合主席AndrewM.Lowy说。"我们可以将癌症细胞去分化为没有任何危害的细胞表型，这项发现十分地鼓舞人心。事实上，先前已经有细胞分化的治疗方法，成功地用于治疗急性早幼粒细胞白血病（APL）和某些神经细胞瘤。"

"我们的下一步将测试病人的肿瘤样本，看E47是否可以引起相似的结果，从而为抗击这种高致死率的疾病提供新的治疗方法。"Itkin-Ansari说。"此外，我们也将筛选可以引起E47过表达的分子-蛋白药物。"
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胰腺腺癌
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胰腺腺癌是最常见的一种胰腺癌症。这种癌症主要由癌基因Kras突变引起，从而导致了消化酶分泌细胞（腺泡细胞）分化为一种不稳定的导管样细胞类型，这种细胞有致癌性。胰腺腺癌常常被称为"沉默"癌症，因为它极少表现出任何症状，当它引起体重下降，腹痛和黄疸时，往往已经是癌症晚期了。

责任编辑：孔祥滨
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Returning Pancreatic Cancer Cells to Normal

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New research has shown that pancreatic cancer cells can be coaxed to revert back toward normal cells by introducing a protein called E47.

New research has shown that pancreatic cancer cells can be coaxed to revert back toward normal cells by introducing a protein called E47.
A silent disease is often characterized as showing little to no signs or symptoms until the disease has progressed to an advanced stage—pancreatic adenocarcinoma is one such type of disease and accounts for approximately 85% of all pancreatic cancer cases. There are few treatment options for this disease and prognosis is often very poor, yet new research from a collaboration of scientists at the University of California, San Diego, Purdue University, and led by a team at Sanford-Burnham Medical Research Institute (SBMRI) in La Jolla, may provide some much needed hope for the future.
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The researchers were able to observe that pancreatic cancer cells could be coaxed to revert toward a more normal acinar cell phenotype with greatly reduced tumorigenic properties. The investigators achieved this through the addition of the transcription factor E47, which typically controls genes involved in growth and differentiation.

“For the first time, we have shown that overexpression of a single gene can reduce the tumor-promoting potential of pancreatic adenocarcinoma cells and reprogram them toward their original cell type,” said Pamela Itkin-Ansari, Ph.D., adjunct professor in the Development, Aging, and Regeneration Program at SBMRI and senior author on the current study. “Thus, pancreatic cancer cells retain a genetic memory which we hope to exploit.”
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The findings from this study were published recently in Pancreas through an article entitled “The Basic Helix-Loop-Helix Transcription Factor E47 Reprograms Human Pancreatic Cancer Cells to a Quiescent Acinar State With Reduced Tumorigenic Potential.”
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Dr. Itkin-Ansari and her collaborators generated human pancreatic ductal adenocarcinoma cell lines that were able to produce increased levels of E47. What they found was that the high levels of E47 caused the cancer cells to stall in the G0/G1 stage of the cell cycle—shortly thereafter beginning the differentiation process back toward the normal cell phenotype.; m. S$ e7 c; @( f. j
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Additionally, when the SBMRI team transplanted the reprogrammed cancer cells into mice they found the ability of those cells to form tumors was diminished drastically.

“Presently, pancreatic adenocarcinoma is treated with cytotoxic agents, yet the average survival for patients post-diagnosis is merely six months, and the improvements in therapies are measured in days,” explained Andrew M. Lowy, M.D., professor of surgery at UC San Diego Moores Cancer Center and co-chair of the National Cancer Institute’s Pancreatic Cancer Task Force and not a co-author on the current study. “The finding that we can differentiate these cancer cells back to a non-threatening phenotype is encouraging. Indeed, there is a precedent for cell differentiation therapy in that the approach has been used to treat acute promyelocytic leukemia and some neuroblastomas successfully.”

The scientists are optimistic about their work having a transformative effect in the field of pancreatic cancer research, but understand that their results are preliminary and much more work will need to be done to understand the molecular underpinnings of this disease.
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“Our next step is to test primary patient-derived tumor tissue to determine whether E47 can produce similar results, potentially providing a novel therapeutic approach to combating this highly lethal disease,” stated Dr. Itkin-Ansari. “Additionally, we are screening for molecules—potential drugs—that can induce overexpression of E47.”% X: n& d! r: _4 x" p* [& c

http://www.genengnews.com/gen-ne ... to-normal/81251177/