美國芝加哥洛約拉大學(xué)醫(yī)學(xué)研究人員日前表示，他們有望開發(fā)出能縮小皮膚癌腫瘤的藥物,，以此取代外科手術(shù),。藥物的工作原理是開啟癌癥細(xì)胞中的蛋白激酶基因，防止皮膚細(xì)胞轉(zhuǎn)變成癌細(xì)胞,。有關(guān)研究發(fā)表在最新出版的《生物化學(xué)雜志》上,。
美國每年經(jīng)確診的皮膚癌新患者在100萬人以上。根據(jù)新近完成的研究,，每年確診的皮膚癌患者中,，鱗狀上皮癌患者的人數(shù)就有20萬至30萬。鱗狀上皮癌始于表皮上部分,，即皮膚最外層,。患病處主要位于陽光照射較多的人體部位,，如臉部,、耳朵、頸部,、嘴唇和手背,。陽光能夠傷害皮膚細(xì)胞的DNA。當(dāng)DNA出現(xiàn)損傷時,，蛋白激酶通常會被激活以修復(fù)損傷,。然而，如果陽光造成的損傷過于嚴(yán)重而無法修復(fù)時,，蛋白激酶就會指令細(xì)胞死亡,。
健康的細(xì)胞按照細(xì)胞分裂周期生長和分裂。在分裂周期中的幾個“檢查點”上,，細(xì)胞會停止生長和分裂,，以便修復(fù)受損的DNA，然后再進(jìn)入分裂周期的下一步。洛約拉大學(xué)斯特里奇醫(yī)學(xué)院病理系教授米切爾·丹寧博士等人研究發(fā)現(xiàn),，負(fù)責(zé)讓細(xì)胞在分裂前的“檢查點”上停止生長和分裂的是蛋白激酶基因,。在鱗狀上皮癌細(xì)胞中，蛋白激酶基因被關(guān)閉,，于是細(xì)胞不能在“檢查點”正常地修復(fù)受損的DNA,，而直接分裂產(chǎn)生新生的癌細(xì)胞。
目前有多種針對皮膚癌的外科手術(shù)療法,，其中包括簡單切除,、刮除術(shù)和冷凍手術(shù)。多數(shù)療法的皮膚癌治愈率較高,，但是病人需要經(jīng)歷痛苦的手術(shù)過程,。此外，切除大面積的皮膚癌需要進(jìn)行皮膚移植,，留下的疤痕將損壞患者的外形,。
丹寧表示,，名為蛋白激酶抑制劑的這類藥物有潛力通過重新打開蛋白激酶基因而縮小皮膚癌腫瘤,。目前，美國食品和藥物管理局已批準(zhǔn)數(shù)種這類藥物用于治療其他的癌癥,。（生物谷Bioon.com）
生物谷推薦原始出處：
JBC 16, 2009, doi: 10.1074/jbc.M109.055392
The Protein Kinase Cδ Catalytic Fragment Is Critical for Maintenance of the G2/M DNA Damage Checkpoint*
Edward L. LaGory?§, Leonid A. Sitailo§? and Mitchell F. Denning?§?,1
From the ?Molecular and Cellular Biochemistry Program, Department of Cell Biology, Neurobiology, and Anatomy,
?Department of Pathology, and
§Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, Illinois 60153
Protein kinase Cδ (PKCδ) is an essential component of the intrinsic apoptotic program. Following DNA damage, such as exposure to UV radiation, PKCδ is cleaved in a caspase-dependent manner, generating a constitutively active catalytic fragment (PKCδ-cat), which is necessary and sufficient for keratinocyte apoptosis. We found that in addition to inducing apoptosis, expression of PKCδ-cat caused a pronounced G2/M cell cycle arrest in both primary human keratinocytes and immortalized HaCaT cells. Consistent with a G2/M arrest, PKCδ-cat induced phosphorylation of Cdk1 (Tyr15), a critical event in the G2/M checkpoint. Treatment with the ATM/ATR inhibitor caffeine was unable to prevent PKCδ-cat-induced G2/M arrest, suggesting that PKCδ-cat is functioning downstream of ATM/ATR in the G2/M checkpoint. To better understand the role of PKCδ and PKCδ-cat in the cell cycle response to DNA damage, we exposed wild-type and PKCδ null mouse embryonic fibroblasts (MEFs) to UV radiation. Wild-type MEFs underwent a pronounced G2/M arrest, Cdk1 phosphorylation, and induction of apoptosis following UV exposure, whereas PKCδ null MEFs were resistant to these effects. Expression of PKCδ-green fluorescent protein, but not caspase-resistant or kinase-inactive PKCδ, was able to restore G2/M checkpoint integrity in PKCδ null MEFs. The function of PKCδ in the DNA damage-induced G2/M cell cycle checkpoint may be a critical component of its tumor suppressor function.
