近日上海腫瘤研究所李宗海研究員領(lǐng)導(dǎo)的腫瘤生物治療研究組在腫瘤生物治療新靶點(diǎn)的發(fā)現(xiàn)與驗(yàn)證研究領(lǐng)域中獲新的研究進(jìn)展,。相關(guān)研究成果發(fā)表在最新一期的《腫瘤形成》（Neoplasia）雜志上,。
李宗海研究員早年畢業(yè)于湖南醫(yī)科大學(xué)，2005年進(jìn)入上海腫瘤研究所擔(dān)任癌基因及相關(guān)基因國(guó)家重點(diǎn)實(shí)驗(yàn)室生物治療研究組長(zhǎng),。長(zhǎng)期從事腫瘤生物治療研究,，承擔(dān)國(guó)家“十一五”科技重大專項(xiàng)、“973”,、國(guó)家自然科學(xué)基金面上項(xiàng)目,、上海市科委重大及重點(diǎn)科技攻關(guān)項(xiàng)目等課題。在FASEB J, J Biol Chem, Neoplasia, Cancer Immunoloy Immunotherapy, Cancer lett, BioTechniques等雜志發(fā)表論文四十多篇,。
表皮生長(zhǎng)因子受體(EGFR)信號(hào)轉(zhuǎn)導(dǎo)途徑在腫瘤細(xì)胞的增殖,、損傷修復(fù)、侵襲及新生血管形成等方面起重要作用,。近年來(lái)靶向EGFR藥物已成為腫瘤治療的新熱點(diǎn),。全球目前已經(jīng)有四個(gè)針對(duì)EGFR靶向藥物（Cetuximab, Panitumumab, Gefitinib, Erlotinib）用于臨床腫瘤治療，前景看好,。
繼今年初研制出具有自主知識(shí)產(chǎn)權(quán)的表皮生長(zhǎng)因子受體III型變異體單克隆抗體后,，該研究組在表皮生長(zhǎng)因子受體研究領(lǐng)域近期又獲得了新的發(fā)現(xiàn)。博士研究生王海等人在李宗海老師的指導(dǎo)下最近在研究中發(fā)現(xiàn)了一種新的表皮生長(zhǎng)因子受體變異體(de4 EGFR),，該變異體在一些腦膠質(zhì)瘤,、卵巢癌和前列腺癌中有表達(dá)，而在所檢測(cè)的相應(yīng)癌旁組織中沒有表達(dá),，研究還發(fā)現(xiàn)該變異體可顯著促進(jìn)腦膠質(zhì)瘤轉(zhuǎn)移,。
目前該課題組已將該變異體申報(bào)了國(guó)家發(fā)明專利，有望成為有自主知識(shí)產(chǎn)權(quán)的腫瘤治療新靶點(diǎn),。(生物谷 Bioon.com)
生物谷推薦原文出處：
Neoplasia
Identification of an Exon 4-Deletion Variant of Epidermal Growth Factor Receptor with Increased Metastasis-Promoting Capacity1,2
Hai Wang, Min Zhou,Bizhi Shi,Qingli Zhang,Hua Jiang, Yinghao Sun, Jianhua Liu, Keke Zhou,Ming Yao, Jianren Gu,Shengli Yang, Ying Mao,and Zonghai Li
Several types of epidermal growth factor receptor (EGFR) gene alternations have been observed in human tumors. Here we present a novel EGFR variant with aberrant splicing of exon 4 (named as de4 EGFR). Variant-specific polymerase chain reaction showed that de4 EGFR was expressed in some glioma (4/40), prostate cancer (3/11), and ovarian cancer (3/9) tissues but not in tissues adjacent to tumors or normal tissues. de4 EGFR displayed an enhanced transformation and a higher metastasis-promoting capacity in comparison to wild-type EGFR. With minimal EGF-binding activity, de4 EGFR underwent ligand-independent autophosphorylation and self-dimerization. Moreover, in serum-starved condition, de4 EGFR expression in U87 MG cells significantly upregulated the extracellular signal-regulated kinase and AKT phosphorylation and expression of JUN and Src. Importantly, E-cadherin expression was barely detectable in the U87 MG cells expressing de4 EGFR and restored expression of E-cadherin in these cells inhibited their metastatic behaviors. Taken together, we identified a novel EGFR variant with increased metastasis-promoting activity that may become a promising new target for cancer therapy.
