生物谷報(bào)道：最近,，約翰霍普金斯的醫(yī)學(xué)家們發(fā)現(xiàn),，如果因卵巢癌接受治療的女性的腫瘤細(xì)胞具有一種能激發(fā)異常生長和減慢細(xì)胞死亡的(均是惡性腫瘤的標(biāo)志)結(jié)合蛋白，則會(huì)增加快速和潛在致死的危險(xiǎn),。這個(gè)研究的一個(gè)報(bào)告,第一個(gè)把NAC-1和腫瘤聯(lián)系起來,發(fā)表在12月5號(hào)的國家科學(xué)院學(xué)報(bào)上,。
因?yàn)閺?fù)發(fā)的腫瘤經(jīng)常是殺死病人的真正原因,并且大多數(shù)卵巢癌診斷時(shí)已經(jīng)是晚期,這個(gè)發(fā)現(xiàn)給女性一個(gè)抓住或預(yù)防早期復(fù)發(fā)和增加生存的更好的機(jī)會(huì)。根據(jù)研究者們的估計(jì),經(jīng)過初治表現(xiàn)為無病生存的晚期卵巢癌病病人,至少60%出現(xiàn)復(fù)發(fā),。當(dāng)研究者們比較了兩個(gè)醫(yī)院338例卵巢癌初治和復(fù)發(fā)病人的NAC-1水平后發(fā)現(xiàn),同一個(gè)病人復(fù)發(fā)時(shí)的NAC-1水平顯著高于其初治時(shí).初治時(shí)具有高水平的NAC-1病人更可能在一年內(nèi)出現(xiàn)復(fù)發(fā),。為了研究NAC-1的功能,研究者們?cè)谶z傳上修飾了細(xì)胞以便他們使得NAC-1和發(fā)現(xiàn)在自然NAC-1用完時(shí)是一個(gè)結(jié)合位點(diǎn)的這種蛋白的一個(gè)組成.在修飾了的細(xì)胞,N130阻斷了NAC-1蛋白而使它們互相結(jié)合的能力打斷.在小鼠試驗(yàn)中,這種作用能預(yù)防腫瘤形成,殺死癌細(xì)胞。
這項(xiàng)研究揭示：測(cè)試手術(shù)中切除的腫瘤組織中的NAC-1蛋白可能鑒別出大多具有復(fù)發(fā)的女性并指導(dǎo)醫(yī)生和患者更警惕和進(jìn)一步治療,。在將來, 能夠阻斷NAC-1作用的藥物也可能用來治療腫瘤,。
Fig. 4. Coimmunoprecipitation and colocalization of NAC-1 deletion mutants and full-length NAC-1. (A) Diagram of NAC-1 and NAC-1 deletion mutants. Full-length (FL) construct contains V5 tag at the C terminus, whereas all of the deletion mutants contain an Xpress (Xp) tag at the N terminus. The yellow box is the BTB/POZ domain; the blue box is the DUF1172 domain. (B) Coimmunoprecipitation shows that full-length NAC-1, N130, and N250 bind to NAC-1. The predicted molecular masses, not including the tag sequences, are: full-length NAC-1 (57.3 kDa), N130 (14.4 kDa), N250 (27.8 kDa), C250 (30.3 kDa), and M120 (14 kDa). (C) Cells with stable full-length NAC-1/V5 expression were transfected with different deletion mutants with the Xp tag. Double immunofluorescence shows that full-length NAC-1, N130, and N250 deletion mutants colocalize with full-length NAC-1. However, only full-length NAC-1 proteins form discrete round and oval-shaped NAC-1 nuclear bodies, whereas both N130 and N250 form irregular aggregates with the full-length NAC-1. Neither C250 nor M120 colocalizes with the full-length NAC-1 protein.
原文出處：
Kentaro Nakayama, Naomi Nakayama, Ben Davidson, Jim J.-C. Sheu, Natini Jinawath, Antonio Santillan, Ritu Salani, Robert E. Bristow, Patrice J. Morin, Robert J. Kurman, Tian-Li Wang, and Ie-Ming Shih
A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival
PNAS 2006 103: 18739-18744; published online before print November 27 2006, 10.1073/pnas.0604083103
[Abstract] [Full Text] [Figures Only] [PDF]
[Supporting Information]
相關(guān)基因：
LOC382983
similar to NAC-1 protein; transcriptional repressor NAC1 [Mus musculus]
Chromosome: 15; Location: 15 B3.1
GeneID: 382983
This record was discontinued.
作者簡(jiǎn)介：
Ie-Ming Shih, M.D., Ph.D.
Co-Investigator, Career Development Program
Associate Professor
Faculty in Pathobiology
Graduate Program
Department of Pathology
Johns Hopkins University
School of Medicine
1503 E. Jefferson Street
Room B-315
Baltimore, MD 21231
Dr. Shih graduated from Taipei Medical University (previously Taipei Medical Colleage) with an MD degree and from the University of Pennsylvania with a PhD degree in biomedical science. He finished his pathology residency training and gynecologic pathology fellowship (with Dr. Robert J. Kurman) at the Johns Hopkins Hospital. Dr. Shih has been board certified in anatomic pathology since 1997. He has spent 2 years in basic research with Dr. Bert Vogelstein at Johns Hopkins Oncology Center. Currently, Dr. Shih is an associate professor and an attending physician in the Departments of Pathology, Gynecology/obstetrics and Oncology at Johns Hopkins. Dr. Shih's specialty in diagnostic pathology includes all aspects in gynecological pathology, especially in trophoblastic diseases. Dr. Shih's research focuses on molecular genetics in ovarian cancer and translational researches in molecular diagnostics for cancer.
Please visit Dr. Shih's website for detailed research activities:
