生物谷报道：在美国，每年因胰腺癌死亡的人数高达30000，其中在10%的病例中遗传起一定的作用。通常在疾病扩散之后，才能确诊，大多数的病人在1年内死亡。因此，对胰腺癌的发病机理，目前知之甚少。最近，美国的科学家通过对一个胰腺癌高发家族的跟踪研究，发现了一个新的致胰腺癌基因paladin。这一结果最近发表在Science Medicine的Public Library杂志上。
该家族被西雅图的华盛顿大学的胃肠病学家Teri Brentnall称为x家族，10年内9个亲属死于胰腺癌，9个其他亲属出现了癌的前期病变。在广泛的基因分析之后，研究者发现Palladin是负责细胞结构和行动的一个非常重要的复合体中的一个大分子，它的变异影响了palladin与复合体中其他分子的一个关键的结合部位，这一改变似乎使负责细胞形态的结构变得不稳定，从而能使变异细胞自由转移。在该家族中，每一个发现有paladin变异的家族成员都患有胰腺癌或者癌前病变。并且，科学家们也在散发的胰腺癌病人中发现了这种变异。
此外，这个在此家族中得到确认的第一个与胰腺癌有关的变异基因，可能也参与了其他遗传性或非遗传性的肿瘤的产生。尽管如此，该基因与其他遭受胰腺癌折磨的家族或其他非遗传性病例的相互关系和作用程度还有待进一步研究。
Figure 2.Overexpression of Palladin RNA in Sporadic Pancreatic Cancer and in Family X Precancer
(A) To narrow down candidate genes we constructed custom 4q32–34 microarrays composed of 243 expressed sequence tags (IMAGE clones), each of which was spotted six times on the array. The microarrays were hybridized with RNA derived from the following target tissues: sporadic pancreatic adenocarcinoma (n = 10), Family X pancreatic precancer (n = 1), and normal donor pancreas (n = 2). Each target tissue was hybridized separately on the arrays and compared to normal pancreas. This array image is representative of one of the sporadic cancer samples versus normal pancreas. Note the consistency of the expression of the six spotted replicates of cDNA clones. Green indicates genes that were underexpressed in cancer compared to normal pancreas; red indicates genes that were overexpressed in cancer compared to normal pancreas, and yellow indicates genes that were expressed in similar levels as normal pancreas.
(B) The most overexpressed clones among ten sporadic pancreatic cancers were two different palladin clones; both of these clones were significantly overexpressed in Family X precancer.
(C) RNA overexpression of palladin was confirmed by qRT-PCR. Samples tested were whole pancreatic tissues and included six new normal pancreas samples, four new precancerous tissues (PanIN 2 and 3, or low- and high-grade dysplasia, respectively) from two Family X individuals and two unique familial pancreatic cancer individuals not from Family X, nine histologically normal tissues adjacent to cancer, and 16 new pancreatic cancer tissues. In each case, palladin expression was measured relative to the endogenous standardized control, GAPDH. Error bars indicate 1 standard deviation above and below the average. Palladin RNA is overexpressed early in the process of pancreatic neoplasia, as it is overexpressed in normal-appearing tissue adjacent to sporadic cancer, as well as in precancerous pancreatic tissue. In addition, palladin is overexpressed in the precancerous tissue from three different familial pancreatic cancer kindreds (Family X and two other familial pancreatic cancer kindreds).
原文出处：
PLoS Medicine Vol. 3, No. 12, e516 doi:10.1371/journal.pmed.0030516
Palladin Mutation Causes Familial Pancreatic Cancer and Suggests a New Cancer Mechanism
Kay L. Pogue-Geile¤,1 , Ru Chen2 , Mary P. Bronner3, Tatjana Crnogorac-Jurcevic4, Kara White Moyes2, Sally Dowen4, Carol A. Otey5, David A. Crispin2, Ryan D. George1, David C. Whitcomb1,6,7, Teresa A. Brentnall2*
Download
XML (107 KB) PDF - Large (1672 KB) PDF - Small (449 KB) Citation
背景知识：
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030516
· US National Cancer Institute, information on pancreatic cancer for patients and health professionals
· MedlinePlus encyclopedia entry on pancreatic carcinoma
· Cancer Research UK, information for patients about pancreatic cancer
· Johns Hopkins University, information on pancreatic cancer that includes details on familial cancer
· CancerQuest, information provided by Emory University about how cancer develops
相关基因 Pubmed Gene
Palld
Official Symbol: Palld and Name: palladin, cytoskeletal associated protein [Mus musculus]
Other Aliases: 2410003B16Rik, 6030492A02, MGC150248
Other Designations: 90kDa actin-associated protein palladin; palladin
Chromosome: 8; Location: 8 B3.3
GeneID: 72333
PALLD
Official Symbol: PALLD and Name: palladin, cytoskeletal associated protein [Homo sapiens]
Other Aliases: CGI-151, FLJ22190, FLJ38193, FLJ39139, KIAA0992, SIH002
Other Designations: palladin; sarcoma antigen NY-SAR-77
Chromosome: 4; Location: 4q32.3
MIM: 608092
GeneID: 23022
附一篇review中关于palladin的陈述：
肌动蛋白细胞内骨架的动态重塑在细胞的形态形成和细胞的运动方面有重要的作用。此过程中，那些募集与肌动蛋白相关的分子和细胞内的信号复合体的分子的作用极为重要。palladin就属于此家族的新发现的分子。它在脊椎动物的发育中非常常见。对其主要功能的研究，集中于中枢神经系统和组织培养方面。其在细胞形态形成中有重要作用。palladin除了可以和a－actin结合外，还可以结合血管舒张因子刺激的磷蛋白（VASP）和埃兹蛋白。
作者简介：
Teri Brentnall, MD
University of Washington Medical Center
Dr. Brentall is an Associate Professor of Medicine at the University of Washington in Seattle , Washington . Her focus is on tumorigenesis in the gastrointestinal tract with emphasis in 3 areas of research: 1) Molecular events, prevention, and early detection of colon cancer in patients with inflammatory bowel disease, 2) Molecular events and early detection of pancreatic cancer and 3) Surveillance and management of patients who inherit pancreatic cancer.
