کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151391 | 1089988 | 2013 | 24 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
HMGA2 Inhibits Apoptosis through Interaction with ATR-CHK1 Signaling Complex in Human Cancer Cells
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کلمات کلیدی
ATRDDRMMSHmgCICscancer-initiating cellsFLICAataxia telangiectasia mutated - Ataxia telangiectasia جهش یافته استcheckpoint kinase - بازرسی کینازATM - خودپردازMethyl methane sulfonate - متیل متان سولفوناتHydroxyurea - هیدروکسی اورهDNA-dependent protein kinase catalytic subunit - وابسته به DNA وابسته به پروتئین کیناز کاتالیزوریDNA damage response - واکنش به آسیب DNA Chk - چاکhigh mobility group - گروه تحرک بالا
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: HMGA2 Inhibits Apoptosis through Interaction with ATR-CHK1 Signaling Complex in Human Cancer Cells HMGA2 Inhibits Apoptosis through Interaction with ATR-CHK1 Signaling Complex in Human Cancer Cells](/preview/png/2151391.png)
چکیده انگلیسی
The non-histone chromatin binding protein high mobility group AT-hook 2 (HMGA2) is expressed in stem cells and many cancer cells, including tumor initiating cells, but not translated in normal human somatic cells. The presence of HMGA2 is correlated with advanced neoplastic disease and poor prognosis for patients. We had previously demonstrated a role of HMGA2 in DNA repair pathways. In the present study, we employed different human tumor cell models with endogenous and exogenous expression of HMGA2 and show that upon DNA damage, the presence of HMGA2 caused an increased and sustained phosphorylation of the ataxia telangiectasia and Rad3-related kinase (ATR) and its downstream target checkpoint kinase 1 (CHK1). The presence of activated pCHK1Ser296 coincided with prolonged G2/M block and increased tumor cell survival, which was enhanced further in the presence of HMGA2. Our study, thus, identifies a novel relationship between the ATR-CHK1 DNA damage response pathway and HMGA2, which may support the DNA repair function of HMGA2 in cancer cells. Furthermore, our data provide a rationale for the use of inhibitors to ATR or CHK1 and HMGA2 in the treatment of HMGA2-positive human cancer cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 15, Issue 3, March 2013, Pages 263-280, IN8-IN13
Journal: Neoplasia - Volume 15, Issue 3, March 2013, Pages 263-280, IN8-IN13
نویسندگان
Suchitra Natarajan, Sabine Hombach-Klonisch, Peter Dröge, Thomas Klonisch,