EGF，Genistein对垂体瘤细胞膜PI转换的影响

表皮生长因子(epidermal growth factor,EGF)和酪氨酸激酶抑制剂对垂体瘤细胞的增殖和分泌功能有重要影响,其作用机制之一在于对细胞内酪氨酸激酶信号传导通路的调节;同时也发现它们对细胞内第一信使Ca~(2 )水平变化有重要影响。在此,我们对5例垂体瘤的原代培养细胞中磷酰肌醇(phosphatidylinositol,PI)转换率变化进行检测,以探讨EGF、酪氨酸激酶抑制剂Genistein对垂体瘤细胞信号传导调节的交互影响机制。     

肺癌相关信号转导通路的研究进展

信号转导是各类信号通过细胞膜或胞内信使分子引起细胞基因表达改变的过程。因此,当细胞信号转导过程发生障碍或异常,必然会导致细胞生长、分化、代谢及生物学特征异常,从而引起各种疾病甚至肿瘤的发生。目前已知与肺癌相关的细胞信号转导通路有Wnt、Notch、酪氨酸激酶和Hedgehog信号转导通路。现将近年来的研究进展作一综述。     

活性氧调控的细胞凋亡信号

ROS一直被认为是毒性代谢的副产物,是一类损伤细胞的毒性物质。然而随着研究的深入,人们发现ROS是细胞信号通路中的重要中介体,在维持细胞内氧化平衡和细胞信号通路的转导上发挥着重要的作用。近年来关于ROS在细胞凋亡信号中的作用也逐渐受到重视,本文就ROS在凋亡信号中的作用机制作一综述。     

活性氧调控的细胞凋亡信号

ROS一直被认为是毒性代谢的副产物,是一类损伤细胞的毒性物质。然而随着研究的深入,人们发现ROS是细胞信号通路中的重要中介体,在维持细胞内氧化平衡和细胞信号通路的转导上发挥着重要的作用。近年来关于ROS在细胞凋亡信号中的作用也逐渐受到重视,本文就ROS在凋亡信号中的作用机制作一综述。     

肝癌相关细胞信号转导通路的研究进展

0 引言 生物的信号转导足指细胞感知胞外刺激后,通过细胞内信号分子的逐级传递作用,最终诱导产生一系列的细胞质、细胞核内事件和各种生理生化反应的过程.与肝癌有关的细胞信号转导通路有酪氨酸激酶信号转导通路、Notch信号转导通路、核转录因子kappaB(NF-KB)通路、Hedgehog( Hh)信号通路等,现将近年来的研究进展作一综述,并重点阐述酪氨酸蛋白激酶体系在肝癌发病、转移、治疗与耐药中的作用.     

脑胶质瘤细胞中胰岛素样生长因子-1对垂体瘤转化基因表达的调节作用

 目的　探讨在体外培养的脑胶质瘤细胞中,胰岛素样生长因子-1（IGF-1）对垂体瘤转化基因（PTTG）表达的作用及主要途径。方法　原代培养脑胶质瘤细胞,并成功传代。以不同浓度的IGF-1在体外作用于脑胶质瘤细胞,半定量反转录聚合酶链反应（RT-PCR）检测PTTG mRNA的表达;用三磷酸酰肌醇蛋白激酶（PI3K）细胞信号转导通路的蛋白激酶抑制剂（LY294002）在体外作用于脑胶质瘤细胞后,再用IGF-1作用于细胞,然后用RT-PCR检测PTTG mRNA表达。结果　与空白对照组比较,PTTG mRNA的表达在各IGF-1作用组均显著增高,各组间比较差异有统计学意义（P＜0.01）。经LY294002处理后,再加入IGF-1的实验组,与只加有IGF-1的对照组比较,PTTG mRNA的表达显著降低,两组间比较差异有统计学意义（P＜0.01）。结论　IGF-1可以量-效的方式上调PTTG的表达,并主要以PI3K细胞信号转导通路发挥调节作用。     

Notch信号通路与肿瘤

Notch信号通路存在于多种动物体内,脊椎动物中有4个Notch同源体Notch1、Notch2、Notch3、Notch4,其中Notch1在肿瘤形成中起重要作用,至于其是癌基因还是抑癌基因,目前尚存争议.Notch通路是许多重要细胞信号转导通路的交汇点,对Notch1的研究可进一步阐明肿瘤发生的机制,为肿瘤基因治疗及新药开发提供一个新的有希望的靶点.     

MACC1在消化系统肿瘤中的研究进展

MACC1是新近发现的与癌症的发生和发展密切相关的基因,一些细胞信号转导通路或生物分子可能参与了MACC1的表达调控以及MACC1 促进肿瘤侵袭转移的相关机制。由于MACC1在消化系统肿瘤中的高表达,可能使其成为新的判断肿瘤预后和治疗的靶点。本文就消化系统肿瘤中MACC1的研究进展进行综述。     

Notch信号通路与肿瘤

Notch信号通路存在于多种动物体内，脊椎动物中有4个Notch同源体：Notch1、Notch2、Notch3、NotcM，其中Notch1在肿瘤形成中起重要作用，至于其是癌基因还是抑癌基因，目前尚存争议。Notch通路是许多重要细胞信号转导通路的交汇点，对Notch1的研究可进一步阐明肿瘤发生的机制，为肿瘤基因治疗及新药开发提供一个新的有希望的靶点。     

Notch信号通路与肿瘤细胞凋亡的研究进展

Notch信号通路是一种生物进化中高度保守的信号转导通路,在多种细胞的增殖、分化和凋亡中起到关键作用。目前Notch信号通路的配体和受体,以及信号转导途径已经基本研究阐明,有关Notch信号通路与肿瘤细胞凋亡的研究也取得了较大的进展。本文综述了Notch信号通路对血液恶性肿瘤和实体肿瘤细胞凋亡的影响及机制的最新研究结果,重点回顾了Notch信号通路对不同种类肿瘤细胞凋亡的高背景相关性,以及Notch信号通路与其它细胞信号通路之间的串扰,及对肿瘤细胞凋亡的影响。     

哺乳动物雷帕霉素靶蛋白信号通路与大肠癌

哺乳动物雷帕霉素靶蛋白(mTOR)信号通路作为细胞内重要信号转导通路之一,通过影响下游多种效应分子的活化状态,调节细胞存活、增殖、转分化、迁移和细胞周期.mTOR这些调节机制的异常与大肠癌的发生和发展密切相关.目前mTOR抑制剂治疗大肠癌已处于临床试验中,并取得了一定的进展.     

Mechanisms of translational deregulation in human tumors and therapeutic intervention strategies

Analysis of the recurrent genetic aberrations present in human tumors provides insight into how normal cells escape appropriate proliferation and survival cues. Commonly mutated genes encode proteins that monitor DNA damage (e.g., p53), proteins that regulate the cell cycle (such as Rb), and proteins that regulate signal transduction pathways (such as APC, PTEN and Ras). Analysis of the relevant targets and downstream events of these genes in normal and tumor cells will clearly highlight important pathways for tumorigenesis. However, more infrequent mutations are also informative in defining events critical for the process of tumorigenesis, and often delineate important pathways lying downstream of commonly mutated oncogenes and tumor suppressors. Together, these studies have led to the conclusion that deregulated protein synthesis plays an important role in human cancer. This review will discuss the evidence implicating mRNA translation as an important downstream consequence of signal transduction pathways initiated by mutated oncogenes and tumor suppressors, as well as additional genetic findings implicating the importance of global and specific translational control in human cancer. It will also discuss therapeutic strategies that take advantage of differences in translational regulation between normal and tumor cells.     

Targeting Raf/MEK/ERK pathway in pituitary adenomas

Pituitary adenomas are the common neoplasms that cause mass effect and/or endocrine dysfunction. Studies in the pathogenesis and functional regulation of pituitary adenomas are mainly focused on the following two topics: (a) the origin of pituitary adenomas and abnormal physical adjustment due to the activation of oncogenes and loss of function for tumour-suppressor genes; and (b) the mechanistic anomalies of the intracellular signal transduction. Among which, the Raf/MEK/ERK signalling has been considered to be one of the major and central pathways in disease aetiology. Raf/MEK/ERK signalling is evolutionarily conserved that controls cellular growth, differentiation and survival. Altered functionality of this signalling pathway has been found to be involved in the development of several types of cancers in humans including pituitary adenomas. This review summarises the roles of Raf/MEK/ERK signalling pathway in pituitary tumourigenesis and highlights the clinical potential of this signalling pathways to be a therapeutic target for intervention and treatment of pituitary adenomas.     

Radiation-Induced Apoptosis: The Ceramide-SAPK Signaling Pathway and Clinical Aspects

Apoptosis, or programmed cell death is an important regulatory mechanism that is involved in a variety of homeostatic processes. Decreased cellular sensitivity or inappropriate responses to apoptotic stimuli may be important factors in tumorigenesis and resistance to anticancer treatments. It is generally accepted that all mammalian cells constitutively express the biochemical machinery to execute apoptosis. It is, however, not clear which signal transduction pathways are involved, or to which extent various stimuli activate independent or partially overlapping pathways. In this paper we discuss the involvement of a ceramide-mediated stress-activated protein kinase (SAPK) signaling cascade in radiation-induced apoptosis. Furthermore, examples are presented of pharmacological intervention in specific signal transduction pathways that lead to modulation of the apoptotic response. Finally, data are presented to illustrate the potential clinical relevance of apoptosis.     

MAPK 信号通路在肝细胞癌发生发展中的作用

丝裂原活化蛋白激酶（mitogen activated protein kinase,MAPK）信号通路对多种肿瘤的发生发展过程起着重要的调节作用。肝细胞癌（hepatocellular carcinoma,HCC）细胞的凋亡、增殖、侵袭和转移等过程与p38MAPK、ERK、JNK 等 MAPK 信号通路同样有密切联系。本文将从这三条信号转导通路对 MAPK 信号通路在 HCC 发生发展中的作用进行综述。     

Eph受体和Ephrin配体的研究进展

蛋白酪氨酸激酶基因家族是最大的癌基因家族，蛋白酪氨酸激酶参与信号传导通路、控制细胞形态、参与细胞增殖、分化和迁移。本文就Eph受体和Ephrin配体在正常发育过程中的作用以及可能的促进肿瘤生成作用的最新研究进展进行综述。     

Murine mammary gland carcinogenesis is critically dependent on progesterone receptor function.

To define the functional relevance of progesterone-initiated intracellular signaling in mammary gland tumorigenesis, the progesterone receptor knockout (PRKO) mouse model was used in the context of an established carcinogen-induced mammary tumorigenesis system. In carcinogen-treated, 7,12-dimethylbenz(a)anthracene (DMBA), pituitary-isografted mice, there was a marked reduction in mammary tumor incidence in PRKO mice as compared with isogenic wild types (WT). Mammary tumors arose in 12 (60%) of 20 WT mice compared with 3 (15%) of 20 PRKO mice by 44 weeks after the initial DMBA treatment. In the absence of a pituitary isograft, mammary tumors developed in 4 (20%) of 20 WT mice versus 4 (20%) of 20 PRKO mice by 47 weeks. At the time of carcinogen administration, the proliferative index of the pituitary-stimulated WT gland was at least 4-fold higher than similarly treated PRKO glands, supporting the importance of PR-mediated proliferative pathways in the genesis of this tumor type. Unlike the WT gland, the PRKO gland was unable to exhibit alveologenesis in response to pituitary isograft stimulation; thus, DMBA-initiated mammary tumors observed in the PRKO were assumed to be exclusively of ductal origin. Compared with previous tested strains, by 47 weeks, a higher incidence of DMBA-induced ovarian tumors was observed in this mouse strain: (a) 4 (20%) of 20 WT mice and 9 (45%) of 20 PRKO mice with a pituitary isograft; and (b) 10 (50%) of 20 WT mice and 10 (50%) of 20 PRKO mice without a pituitary isograft. Despite the host-strain's underlying propensity for DMBA-induced ovarian neoplasms, our studies underscore the specific importance of the PR (as distinct from the estrogen receptor) as a mandatory mediator for those intracellular signaling pathways that are essential for the initiation of the majority of murine mammary tumors induced by DMBA. Apart from providing strong support for progesterone's role in mammary gland tumorigenesis as well as furthering our fundamental understanding of breast cancer etiology, these studies may have implications for the routine use of progestins.     

Deficiency in the gap junction protein connexin32 alters p27Kip1 tumor suppression and MAPK activation in a tissue-specific manner

Connexin32 knockout mice (Cx32-KO) exhibit increased chemical- and radiation-induced liver and lung tumor formation with many lung tumors demonstrating decreased levels of the tumor suppressor p27KIP1. To determine if p27 deficiency alters Cx32-influenced tumorigenesis, we have generated a Cx32/p27 double-deficient mouse strain (DKO) and show here that exposure of these mice to X-ray radiation resulted in an increase or decrease in tumorigenesis depending on the tissue. Several tissues were highly sensitive to loss of p27 tumor suppressor function (intestine, adrenal, pituitary) resulting in an increased overall tumor burden in DKO mice compared to both wild-type (P<0.005) and Cx32-KO mice (P=0.066). However, additional deletion of p27 in a Cx32-KO background resulted in a statistically significant decrease in the liver tumor incidence suggesting that Cx32 and p27 pathways mechanistically interact. Immunohistochemical analysis revealed an increased percentage of Cx32-KO liver and lung tumors harboring active mitogen-activated protein kinase (Erk1, Erk2) pathways in contrast to lower percentages of activated wild-type (P<0.005) and DKO tumors (P=0.027). Increased MAPK activation in liver tumors did not correlate with Ha-ras codon-61 mutation status. This study demonstrates that tissues dependent on Cx32 tumor suppression, such as the liver and lung, exhibit altered tumorigenesis and tumor biology (MAPK pathway activation) related to p27 status.