ROLE OF CELL AND TISSUE STRUCTURE IN NEGATIVE GROWTH REGULATION

发展和分化的过程受以下因素影响 由细胞的结构网络产生的化学机械力。 细胞结构网络包括相互连接的胞外 基质、细胞黏附分子、细胞骨架和核基质。 多项研究支持这些组成部分在发展和发展中的作用 差异化。细胞结构成分的变化 通常伴随着肿瘤进展，尽管这些重要的 肿瘤细胞失去生长控制的改变很差 明白了。我们实验室的最新发现表明有一种肿瘤 细胞生长反应的内在阻断中的抑制基因产物 细胞形状的条件下的生长因子信号-或 依恋。丢失肿瘤抑制基因(supB-)的细胞 不表现出独立于锚定的自主增长，而是在软增长中增长 琼脂中含有血清和生长因子。保留肿瘤的细胞 抑制能力(supb+)在琼脂中生长被抑制，即使在 生长因子的存在，尽管生长因子受体的数量和 SupB4和supb-cell的亲和力是相同的。这两种类型的细胞都在生长 同样，在塑料衬底上存在和不存在附加的 生长因子，说明阻断生长因子对生长因子的调节 SupB+细胞的有丝分裂与细胞形状或附着有关。这个 SuB-细胞表现出表达和组织的变化 细胞结构网络的几个组成部分，包括肌动蛋白 细胞骨架、细胞黏附分子、细胞外基质分子和 可能是核矩阵。我们的工作假设是 SUB细胞中肿瘤抑制基因的失活导致 观察到的结构变化和细胞形状依赖的差异 在生长和基因表达方面表现为SuB-细胞直接 与这些结构性扰动有关。改变后的细胞结构， 与锚定无关的生长和基因表达模式相关 随着肿瘤抑制表型的丧失，这些细胞中可能 说明了与细胞形状、分化 和癌症。

The process of development and differentiation are influenced by chemomechanical forces generated by the structural network of the cell. The cell structural network includes the interconnected extracellular matrix, cell adhesion molecules, cytoskeleton, and nuclear matrix. Multiple studies support the role of these components in development and differentiation. Alterations in the structural components of the cell often accompany neoplastic progression although the significance of these changes to loss of growth controls in neoplastic cells is poorly understood. Recent findings from our laboratory implicate a tumor suppressor gene product in an intrinsic block of cellular growth responses to growth factor signals under conditions that are cell shape- or attachment-dependent. Cells that have lost a tumor suppressor gene (supB-) do not exhibit autonomous anchorage-independent growth but grow in soft agar in the presence of serum and growth factors. Cells that retain tumor suppressing ability (supb+) are growth inhibited in agar even in the presence of growth factors, although growth factor receptor numbers and affinities are the same for supB4 and supb- cells. Both cell types grow similarly on a plastic substrate in the presence and absence of additional growth factors, indicating that the block to growth factor mediated mitogenesis in supB+, cells is related to cell shape or attachment. The supB- cells exhibit alterations in the expression and organization of several components of the cell structural network, including the actin cytoskeleton, cell adhesion molecules, extracellular matrix molecules, and possibly the nuclear matrix. Our working hypothesis is that loss of inactivation of a tumor suppress gene in the supB- cells results in the observed structural changes and that the cell shape-dependent differences in growth and gene expression manifest by the supB- cells are directly related to these structural perturbations. The altered cell structure, anchorage-independent growth, and patterns of gene expression the correlate with loss of the tumor suppressor phenotype in these cells may be illustrative of a general mechanism relating cell shape, differentiation, and cancer.