B-MYC REGULATION AND FUNCTION

我们的长期目标是确定B-myc在这一过程中的作用 对细胞生长、细胞凋亡和癌症的影响。我们的初步研究 显示B-myc在相对较高的水平上表达- 受控制的组织。与c-myc不同，B-myc是区域性表达的 并被睾丸素停用显著下调 附睾症。它似乎也受到雌激素的下调。 子宫，而c-myc被雌激素上调。有趣的是，B-myc 在多种致瘤细胞系中未检测到表达或 在原发的小鼠前列腺癌中，表明在肿瘤中起到了作用 压制。进一步支持B-myc在生长抑制中的作用 和肿瘤抑制，B-myc的过表达显著抑制 细胞增殖和拮抗c-Myc的能力 刺激细胞增殖，但不是细胞凋亡。最后，有了 我们产生的特定B-myc抗体，我们已经识别并 鉴定了小鼠组织中的B-Myc蛋白。我们的假设是 B-Myc是一种高度受调控的myc家族成员，在生长发育中发挥作用 抑制和肿瘤抑制，特别是在激素控制的情况下 组织，作为c-Myc和其他生长刺激剂的拮抗剂 转录因子。我们将在以下几个方面验证这一假设 具体目的：1)检测B-myc在致瘤细胞中的表达 与正常细胞相比。B-myc高速公路的损失将是 在致瘤细胞系和转基因前列腺中进行的研究 癌症模型。B-myc在体外和体外表达的特异性细胞类型 活体也将在正常细胞和组织中进行检测；2)检测 B-myc在小鼠和大鼠体内表达的激素和发育调节 组织，并确定B-myc在生长过程中是否受到调控， 在选定的细胞系中进行分化或凋亡；3)检查 B-myc作为生长抑制因子和肿瘤抑制因子的功能 在选定的细胞系中过表达并评价B-myc的作用 通过产生B-myc缺失小鼠而在体内丢失；以及4)检查 B-myc的作用机制。B-Myc与临界c-Myc的相互作用 将对结合蛋白进行研究。

Our long term goal is to determine the role of B-myc in the processes of cell growth, apoptosis and carcinogenesis. Our preliminary studies show that B-myc is expressed at relatively high levels in harmonally- controlled tissues. In contrast to c-Myc, B-myc is regionally expressed and dramatically downregulated by testosterone withdrawal in the epididymis. It also appears to be downregulated by estrogen in the uterus, while c-myc is up-regulated by estrogen. Interestingly, B-myc expression was not detected in a variety of tumorigenic cell lines or in a primary mouse prostate tumor, suggesting a role in tumor suppression. Further supporting a role for B-myc in growth inhibition and tumor suppression, overexpression of B-myc significantly inhibits cellular proliferation and antagnonizes the ability of c-Myc to stimulate cellular proliferation, but not apoptosis. Finally, with specific B-myc antibodies we have generated, we have identified and characterized the B-Myc protein in mouse tissue. Our hypothesis is that B-Myc is a highly-regulated myc family member which has a role in growth inhibition and tumor suppression, especially in hormonally-controlled tissues, as an antagonist of c-Myc and perhaps other growth stimulatory transcription factors. We will test this hypothesis in the following specific aims: 1) Examine the expression of B-myc in tumorigenic cells compared to normal cells. The loss of B-myc expresssion will be investigated in tumorigenic cell lines and in a transgenic prostate cancer model. The specific cell types expressing B-myc in vitro and in vivo will also be examined in normal cells and tissues; 2) Examine the hormonal and devlopmental regulation of B-myc expression in mice and rat tissues and determine if B-myc is regulated during growth, diferentiation or apoptosis in selected cell lines; 3) Examine the function of B-myc as a growth inhibitor and tumor suppressor by overexpression in selected cell lines and evaluate the effects of B-myc loss in vivo by generating a B-myc null mouse; and 4) Examine the mechanism of B-myc action. The interaction of B-Myc with critical c-Myc binding proteins will be investigated.