PNAS:与卵巢癌复发相关的凝集蛋白被发现

生物谷

生物谷报道：最近，约翰霍普金斯的医学家们发现，如果因卵巢癌接受治疗的女性的肿瘤细胞具有一种能激发异常生长和减慢细胞死亡的(均是恶性肿瘤的标志)结合蛋白，则会增加快速和潜在致死的危险。这个研究的一个报告,第一个把NAC-1和肿瘤联系起来,发表在12月5号的国家科学院学报上。

因为复发的肿瘤经常是杀死病人的真正原因,并且大多数卵巢癌诊断时已经是晚期,这个发现给女性一个抓住或预防早期复发和增加生存的更好的机会。根据研究者们的估计,经过初治表现为无病生存的晚期卵巢癌病病人,至少60%出现复发。当研究者们比较了两个医院338例卵巢癌初治和复发病人的NAC-1水平后发现,同一个病人复发时的NAC-1水平显著高于其初治时.初治时具有高水平的NAC-1病人更可能在一年内出现复发。为了研究NAC-1的功能,研究者们在遗传上修饰了细胞以便他们使得NAC-1和发现在自然NAC-1用完时是一个结合位点的这种蛋白的一个组成.在修饰了的细胞,N130阻断了NAC-1蛋白而使它们互相结合的能力打断.在小鼠试验中,这种作用能预防肿瘤形成,杀死癌细胞。

这项研究揭示：测试手术中切除的肿瘤组织中的NAC-1蛋白可能鉴别出大多具有复发的女性并指导医生和患者更警惕和进一步治疗。在将来, 能够阻断NAC-1作用的药物也可能用来治疗肿瘤。

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.

原文出处：

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]

相关基因：

LOC382983

similar to NAC-1 protein; transcriptional repressor NAC1 [Mus musculus]

Chromosome: 15; Location: 15 B3.1

GeneID: 382983

This record was discontinued.

作者简介：

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.