生物谷報(bào)道：在美國,，每年因胰腺癌死亡的人數(shù)高達(dá)30000,，其中在10%的病例中遺傳起一定的作用。通常在疾病擴(kuò)散之后,，才能確診,，大多數(shù)的病人在1年內(nèi)死亡。因此,，對(duì)胰腺癌的發(fā)病機(jī)理,，目前知之甚少。最近,，美國的科學(xué)家通過對(duì)一個(gè)胰腺癌高發(fā)家族的跟蹤研究,，發(fā)現(xiàn)了一個(gè)新的致胰腺癌基因paladin。這一結(jié)果最近發(fā)表在Science Medicine的Public Library雜志上,。
該家族被西雅圖的華盛頓大學(xué)的胃腸病學(xué)家Teri Brentnall稱為x家族,，10年內(nèi)9個(gè)親屬死于胰腺癌，9個(gè)其他親屬出現(xiàn)了癌的前期病變,。在廣泛的基因分析之后,，研究者發(fā)現(xiàn)Palladin是負(fù)責(zé)細(xì)胞結(jié)構(gòu)和行動(dòng)的一個(gè)非常重要的復(fù)合體中的一個(gè)大分子，它的變異影響了palladin與復(fù)合體中其他分子的一個(gè)關(guān)鍵的結(jié)合部位,，這一改變似乎使負(fù)責(zé)細(xì)胞形態(tài)的結(jié)構(gòu)變得不穩(wěn)定,，從而能使變異細(xì)胞自由轉(zhuǎn)移。在該家族中,，每一個(gè)發(fā)現(xiàn)有paladin變異的家族成員都患有胰腺癌或者癌前病變,。并且，科學(xué)家們也在散發(fā)的胰腺癌病人中發(fā)現(xiàn)了這種變異,。
此外,，這個(gè)在此家族中得到確認(rèn)的第一個(gè)與胰腺癌有關(guān)的變異基因,，可能也參與了其他遺傳性或非遺傳性的腫瘤的產(chǎn)生。盡管如此,，該基因與其他遭受胰腺癌折磨的家族或其他非遺傳性病例的相互關(guān)系和作用程度還有待進(jìn)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).
原文出處：
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*
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背景知識(shí)：
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
相關(guān)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中關(guān)于palladin的陳述：
肌動(dòng)蛋白細(xì)胞內(nèi)骨架的動(dòng)態(tài)重塑在細(xì)胞的形態(tài)形成和細(xì)胞的運(yùn)動(dòng)方面有重要的作用。此過程中,，那些募集與肌動(dòng)蛋白相關(guān)的分子和細(xì)胞內(nèi)的信號(hào)復(fù)合體的分子的作用極為重要,。palladin就屬于此家族的新發(fā)現(xiàn)的分子。它在脊椎動(dòng)物的發(fā)育中非常常見,。對(duì)其主要功能的研究,，集中于中樞神經(jīng)系統(tǒng)和組織培養(yǎng)方面。其在細(xì)胞形態(tài)形成中有重要作用,。palladin除了可以和a－actin結(jié)合外,，還可以結(jié)合血管舒張因子刺激的磷蛋白（VASP）和埃茲蛋白。
作者簡介：
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.
