분자유전학실험실 (단국대학교 분자생물학과)



 이성욱 ( 2015-06-23 19:02:48 , Hit : 876
 A single gene turns colorectal cancer cells back into normal tissue in mice


Public Release: 18-Jun-2015
Cell Press



Credit: Kevin P. O'Rourke


Anti-cancer strategies generally involve killing off tumor cells. However, cancer cells may instead be coaxed to turn back into normal tissue simply by reactivating a single gene, according to a study published June 18th in the journal Cell. Researchers found that restoring normal levels of a human colorectal cancer gene in mice stopped tumor growth and re-established normal intestinal function within only 4 days. Remarkably, tumors were eliminated within 2 weeks, and signs of cancer were prevented months later. The findings provide proof of principle that restoring the function of a single tumor suppressor gene can cause tumor regression and suggest future avenues for developing effective cancer treatments.

Colorectal cancer is the second leading cause of cancer-related death in developed countries, accounting for nearly 700,000 deaths worldwide each year. "Treatment regimes for advanced colorectal cancer involve combination chemotherapies that are toxic and largely ineffective, yet have remained the backbone of therapy over the last decade," says senior study author Scott Lowe of the Memorial Sloan Kettering Cancer Center.

Up to 90% of colorectal tumors contain inactivating mutations in a tumor suppressor gene called adenomatous polyposis coli (Apc). Although these mutations are thought to initiate colorectal cancer, it has not been clear whether Apc inactivation also plays a role in tumor growth and survival once cancer has already developed.

"We wanted to know whether correcting the disruption of Apc in established cancers would be enough to stop tumor growth and induce regression," says first author Lukas Dow of Weill Cornell Medical College. This question has been challenging to address experimentally because attempts to restore function to lost or mutated genes in cancer cells often trigger excess gene activity, causing other problems in normal cells.

To overcome this challenge, Lowe and his team used a genetic technique to precisely and reversibly disrupt Apc activity in a novel mouse model of colorectal cancer. While the vast majority of existing animal models of colorectal cancer develop tumors primarily in the small intestine, the new animal model also developed tumors in the colon, similar to patients. Consistent with previous findings, Apc suppression in the animals activated the Wnt signaling pathway, which is known to control cell proliferation, migration, and survival.

When Apc was reactivated, Wnt signaling returned to normal levels, tumor cells stopped proliferating, and intestinal cells recovered normal function. Tumors regressed and disappeared or reintegrated into normal tissue within 2 weeks, and there were no signs of cancer relapse over a 6-month follow-up period. Moreover, this approach was effective in treating mice with malignant colorectal cancer tumors containing Kras and p53 mutations, which are found in about half of colorectal tumors in humans.

Although Apc reactivation is unlikely to be relevant to other types of cancer, the general experimental approach could have broad implications. "The concept of identifying tumor-specific driving mutations is a major focus of many laboratories around the world," Dow says. "If we can define which types of mutations and changes are the critical events driving tumor growth, we will be better equipped to identify the most appropriate treatments for individual cancers."

For their own part, Lowe and his team will next examine the consequences of Apc reactivation in tumors that progress beyond local invasion to produce distant metastases. They will also continue to investigate why Apc is so effective at suppressing colon tumor growth, with the goal of one day mimicking this effect with drug treatments.

"It is currently impractical to directly restore Apc function in patients with colorectal cancer, and past evidence suggests that completely blocking Wnt signaling would likely be severely toxic to normal intestinal cells," Lowe says. "However, our findings suggest that small molecules aimed at modulating, but not blocking, the Wnt pathway might achieve similar effects to Apc reactivation. Further work will be critical to determine whether WNT inhibition or similar approaches would provide long-term therapeutic value in the clinic."


Cell, Dow et al.: "Apc restoration promotes cellular differentiation and reestablishes crypt homeostasis in colorectal cancer."

http://dx.​doi.​org/​10.​1016/​j.​cell.​2015.​05.​033







1067   혈액 암과 면역세포의 DNA 편집의 관계  이성욱 2015/09/14 881
1066   아스피린이 암의 면역요법 효과 증대  이성욱 2015/09/08 770
1065   처음으로 밝혀진 수면부족과 감기 간의 관련성  이성욱 2015/09/03 806
1064   알츠하이머 질환에 대한 항체약물의 가능성  이성욱 2015/07/30 953
1063   DNA 앰블런스  이성욱 2015/07/30 898
1062   유전자 넉아웃을 보상하는 또 다른 유전자  이성욱 2015/07/30 1137
1061   FDA approves hepatitis C drugs from AbbVie, Bristol-Myers  이성욱 2015/07/28 828
1060   항-PD-1 항체에 저항성을 보이는 기작  이성욱 2015/07/28 994
1059   항체 함암제를 테스트할 수 있는 인간화 생쥐 모델  이성욱 2015/07/28 1247
1058   생명과학 연구에서 암컷쥐가 필요한 이유  이성욱 2015/07/23 907
1057   제 3 자의 혈액을 이용한 T 세포 면역치료  이성욱 2015/07/22 1001
1056   Gene Therapy Allows Beethoven Mouse to Hear  이성욱 2015/07/10 774
1055    기능 향상에 효과를 입증한 낭포성 섬유증 환자들에 대한 첫번째 유전자 요법  이성욱 2015/07/07 1227
1054   프리온 유사 단백질이 장기 기억을 유지시킨다고?  이성욱 2015/07/06 1260
1053   韓中 연구진, TALEN 기술로 초근육질 돼지 만들어  이성욱 2015/07/02 1113
1052   microRNA가 췌장암 치료제가 될 수 있을까  이성욱 2015/06/30 964
1051   T 세포 면역 치료를 향상시키는 유전자  이성욱 2015/06/29 1923
  A single gene turns colorectal cancer cells back into normal tissue in mice  이성욱 2015/06/23 876
1049   프리온 질환을 막는 유전자 돌연변이  이성욱 2015/06/15 902
1048   한국의 MERS가 글로벌 보건을 위협할 수 있을까?  이성욱 2015/06/09 859

[이전 10개] [1].. 11 [12][13][14][15][16][17][18][19][20]..[64] [다음 10개]
 

Copyright 1999-2020 Zeroboard / skin by ROBIN