EGF-R MODULATION AND RESPONSES IN COLON CARCINOMA

EGF-R在结肠癌中的调节和反应-这项研究提出 本申请将研究表皮生长因子的作用 受体（EGF-R）和转化生长因子-α（TGF-α）水平 表达对个体人结肠肿瘤生长特性的影响 细胞系被分为三类， 它们的生物学特性。 这三种细胞系类别利用 一个超过20种人类结肠肿瘤细胞系的库， 在化学成分确定的无血清培养基中生长， 根据它们的分化程度，致瘤性， 在软琼脂糖中生长并产生粘蛋白。 EGF-R与 表达和TGF-α产生对细胞生长的影响将通过 确定结肠肿瘤中受体和因子表达水平 细胞系的生长速度和分化程度差异很大， 通过改变外源性TGF-α和/或表皮生长因子的水平， 生长因子（EGF），以及通过调节功能性EGF的水平 受体在至少两个细胞系中的每一个来自两个最 这3类人结肠肿瘤细胞系在表型上是不同的。 本研究将重点关注以下问题：（一）做得更快 生长中的结肠肿瘤细胞系表达更多的功能性TGF-α，（ii）是 细胞表面EGF-R水平与EGF-RmRNA水平直接相关 （iii）TGF-α和EGF在活化细胞因子的能力上是否不同？ EGF-R酪氨酸特异性蛋白激酶活性，（iv）TGF-α和EGF 不同的是它们产生不同氨基位点的能力 酸性磷酸化的EGF-R，以及（v）如何改变EGF-R的数量 和功能影响结肠细胞的生长和分化？ 受此 更好地理解自然水平之间的关系 TGF-α/EGF-R表达与结肠肿瘤细胞生长特性的关系将 实现。 此外，EGF-R数量对基底细胞的影响 生长、细胞生长要求和分化程度， 将确定单个结肠细胞系类别。

EGF-R Modulation and Responses in Colon Carcinoma - The research proposed in this application will examine the role of epidermal growth factor receptor (EGF-R) and transforming growth factor-alpha (TGF-a) levels of expression upon the growth characteristics of individual human colon tumor cell lines that have been grouped into three classes that are based upon their biological characteristics. These three cell line classes draw upon a bank of more than 20 human colon tumor cell lines that have been adapted to growth in chemically defined, serum-free medium and have been characterized in terms of their extent of differentiation, tumorigenicity, growth in soft agarose and production of mucins. The relationship of EGF-R expression and TGF-a production to cell growth will be studied by determining the levels of receptor and factor expression in colon tumor cell lines that diverge widely in their growth rate and extent of differentiation, by varying the level of exogenous TGF-a and/or epidermal growth factor (EGF), as well as by modulating the levels of functional EGF receptor in at least two cell lines from each of the two most phenotypically divergent of the 3 classes of human colon tumor cell lines. This study will focus upon the following questions: (i) do the faster growing colon tumor cell lines express more functional TGF-a, (ii) is the level of cell-surface EGF-R directly related to level of EGF-R mRNA expression, (iii) do TGF-a and EGF differ in their capacity to activate EGF-R tyrosine specific protein kinase activity, (iv) do TGF-a and EGF differ with regard to their capacity to produce different sites of amino acid phosphorylation of the EGF-R, and (v) how does altered EGF-R number and function influence colon cell growth and differentiation? By this approach a better understanding of the relationship between natural levels of TGF-a/EGF-R expression and colon tumor cell growth characteristics will be achieved. Furthermore, the influence of EGF-R number on the basal cell growth, cell growth requirements, and extent of differentiation for individual colon cell line classes will be determined.