IDENTIFICATION OF ERES IN THE AMPHIREGULIN GENE

描述(申请人的描述)： 申请人在此授权期内的主要目标是发展 成为一名富有成效的独立调查员的技能和能力 以获得持续的资金来支持她自己的研究计划。她 预计她将在Maihle博士的 实验室也将带来未来的协作互动。这些 将通过参加：动手研讨会来发展技能 在分子生物学技术，杂志俱乐部，研讨会，科学 会议，并通过与该领域的其他科学家的互动。 明尼苏达州梅奥诊所的肿瘤生物学课程为她提供了 为实现这一目标提供了出色的学术环境。建议数 研究性学习将为她提供掌握常用语言的机会 肿瘤生物学的研究方法。乳腺癌，最常见的癌症之一 女性中常见的癌症，可能对其发生和生长都有影响 荷尔蒙因素。患者的荷尔蒙环境已被证明会影响 乳腺癌的临床病程。雌激素在卵巢癌中的作用 对乳腺癌细胞系细胞生长的刺激依赖于 存在功能活跃的雌激素受体。此外，失去了 雌激素受体反应性与激素生长相关 乳腺癌细胞系的独立性，并伴随着恶性进展和 预后不良。雌激素促进生长的作用机制是 人们对此知之甚少。然而，据推测，雌激素可能起作用， 至少在一定程度上，通过内生生产的增长因素 可能以自分泌/旁分泌或旁分泌的方式发挥作用。在Dr。 Maihle的实验室，已经证明了一个GF/GFR电路是 受雌激素和雄激素的共同调节，即非调节素/表皮 生长因子受体途径(AR/EGFR)。这些基因的合成 已经证明，产物在mRNA和蛋白质水平上都受到调控。 Maihle博士和其他人已经证明了对EGFR合成的调节 发生在转录水平。此外，它还被重新编排 雌激素在转录水平刺激AR mRNA的诱导 雌激素反应细胞中的水平。在本申请中，申请人 建议检验类固醇诱导AR机制的假说 激素发生在转录水平，类固醇的作用 通过AR/EGFR调节乳腺癌细胞生长 路径。为了检验这一假说，他们建议确定 雌激素对乳腺癌中EGFR、AR和转化生长因子-αmRNAs的诱导 细胞，并鉴定和表征雌激素反应元件在 AR基因。

DESCRIPTION (Applicant's Description): The main goal of the applicant during this award period is to develop the skills and the ability to become a productive, independent investigator able to obtain continuous funding to support her own research program. She anticipates that the research foundation she will develop in Dr. Maihle's laboratory will result in future collaborative interactions as well. These skills will be developed through the participation in: hands-on workshops in molecular biology techniques, journal clubs, seminars, scientific meetings, and through the interaction with other scientists in the field. The Tumor Biology Program at the Mayo Clinic, MN provides her with an outstanding academic environment to accomplish this goal. The proposed research study will provide her the opportunity to master the commonly used research approaches in tumor biology. Breast carcinoma, one of the most common cancers in women, may have both its genesis and growth influence by hormonal factors. Patient's hormonal environment has been shown to affect the clinical course of breast cancer. The effect of estrogen in the stimulation of cell growth in breast cancer cell lines depends on the presence of active functional estrogen receptors. Moreover, the loss of estrogen receptor responsiveness is associated with hormone growth independence in breast cancer cell lines, and with malignant progression and poor prognosis. The mechanism of estrogen action in growth stimulation is poorly understood. However, it has been postulated that estrogen may act, at least in part, through the endogenous production of growth factors that may function in an autocrine/paracrine or juxtacrine manner. In Dr. Maihle's laboratory, it has been demonstrated that one GF/GFR circuit is regulated by both estrogen and androgen, i.e., the a m phiregulin/epidermal growth factor receptor pathway (AR/EGFR). The synthesis of these gene products has been shown to be regulated at both mRNA and protein levels. Dr. Maihle and others have shown that regulation of the EGFR synthesis occurs at the transcriptional level. In addition, it has been r e p orted that estrogen stimulates the induction of AR mRNA at the transcriptional level in estrogen responsive cells. In this application the applicants propose to test the hypothesis that the mechanism of AR induction by steroid hormones occurs at the transcriptional level and that the action of steroids in the regulation of breast carcinoma cell growth is through the AR/EGFR pathway. To test this hypothesis they propose to determine the kinetics of induction of EGFR, AR, and TGF-alpha mRNAs by estrogen in breast carcinoma cells and to identify and characterize the estrogen response elements in the AR gene.