INDUCTION OF MAMMARY CANCER BY SIGNALING MOLECULES

描述：(改编自申请者的摘要)乳腺 代表着一个独特的发展系统，在这个系统中，重大的发展事件 发生在出生后。乳腺的出生后发育发生在 对各种生长因子(表皮生长因子， 胰岛素样生长因子L、生长激素和催乳素)，以及类固醇 雌激素和黄体酮。细胞的增殖和分化 乳腺上皮细胞不是连续的，两者都发生在波浪式的 增殖之后是一波又一波的程序性细胞死亡。程控单元 死亡或细胞凋亡发生在青春期，因为末端芽退缩和凹陷。 导管是形成的，在退化期间也会形成大量的乳房 上皮细胞死亡，组织发生重塑。PI假设 在这两个发育点中的任何一个抑制细胞凋亡将导致 发育异常，最终导致乳腺癌。这一假设 将使用转基因小鼠进行测试。调查人员表示， 抗细胞凋亡蛋白激酶Akt的组成性激活形式 (MYR-Akt)基因在转基因小鼠乳腺中的表达及其对小鼠免疫功能的影响 乳腺发育。他们还将开发出转基因小鼠，以表达 乳腺中催乳素受体D178的一种结构性激活形式 老鼠的腺体。Myr-Akt小鼠将测试Akt是否是 乳腺上皮细胞的凋亡。他们假设Myr-Akt会推迟 退化，但不会诱发肿瘤。表达结构性激活的小鼠 催乳素受体将测试该受体是否能提供有丝分裂 向乳腺上皮细胞发出信号，以及抑制细胞凋亡。我们相信 激活的催乳素受体通过以下方式改变乳腺发育 诱导处女小鼠的花朵发育。我们还预计，它将导致 乳腺肿瘤。这些转基因小鼠将被用来鉴定癌基因。 以及能够与Myr-Akt或Myr-Akt合作的肿瘤抑制基因 催乳素受体D178缺失突变在诱发乳腺癌中的作用 这些研究将为催乳素的作用提供新的信息 受体在乳腺上皮细胞上的表达，以及细胞凋亡是否受到抑制 在乳腺癌的发生中起重要作用。

DESCRIPTION: (Adapted from the applicant's abstract) The mammary gland represents a unique developmental system in which major developmental events occur after birth. Postnatal development of the mammary gland occurs in response to stimulation with various growth factors (epidermal growth factor, insulin like growth factor l, growth hormone, and prolactin), and the steroid hormones estrogen and progesterone. The proliferation and differentiation of mammary epithelial cells is not continuous, both rather occur in waves of proliferation followed by waves of programmed cell death. Programmed cell death, or apoptosis, occurs during puberty as the end buds regress and hollow ducts are formed, as well as during involution when massive numbers of mammary epithelial cells die and tissue remodeling occurs. PI hypothesize that suppression of apoptosis at either of these developmental points will result in developmental abnormalities, and eventually in mammary cancer. This hypothesis will be tested using transgenic mice. Investigators have expressed a constitutively activated form of the anti-apoptotic protein kinase Akt (Myr-Akt) in the mammary gland of transgenic mice and determine its effect upon mammary gland development. They will also develop transgenic mice that express a constitutively activated form of the prolactin receptor 'D178) in the mammary gland of mice. The Myr-Akt mice will test whether Akt is a central regulator of apoptosis in mammary epithelial cells. They hypothesize that Myr-Akt will delay involution but not induce tumors. Mice expressing the constitutively activated prolactin receptor will test whether this receptor can provide a mitogenic signal to mammary epithelial cells, as well as suppress apoptosis. We believe that the activated prolactin receptor will alter mammary gland development by inducing florid development in virgin mice. We also expect that it will induce mammary tumors. These transgenic mice will then be used to identify oncogenes and tumor suppressor genes that are able to cooperative with either Myr-Akt or the D178 deletion mutant of the prolactin receptor in inducing mammary cancer. These studies will provide new information about the effect of the prolactin receptor upon mammary epithelial cells, and whether suppression of apoptosis in Important in mammary carcinogenesis.