ROLE OF CELL AND TISSUE STRUCTURE IN NEGATIVE GROWTH REGULATION

发育和分化的过程受 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细胞外 基质、细胞粘附分子、细胞骨架和核基质。 多项研究支持这些成分在发展中的作用， 分化 细胞结构成分的改变 通常伴随着肿瘤进展，尽管这些 肿瘤细胞生长控制丧失的变化 明白 我们实验室最近的发现表明 抑制基因产物在细胞生长反应内在阻断中的作用 生长因子信号的条件下，细胞的形状-或 依赖于附件。 失去肿瘤抑制基因（supB-）的细胞 不表现出自主的锚定独立的增长，但增长在软 琼脂在血清和生长因子的存在下。 保留肿瘤的细胞 抑制能力（supb+）在琼脂中生长受到抑制， 生长因子的存在，虽然生长因子受体的数量和 对supB 4和supB-细胞的亲和力是相同的。 两种细胞都能生长 类似地，在存在和不存在另外的 生长因子，表明阻断生长因子介导 supB+细胞中的有丝分裂与细胞形状或附着有关。 的 supB-细胞表现出在表达和组织的改变， 细胞结构网络的几个组成部分，包括肌动蛋白 细胞骨架，细胞粘附分子，细胞外基质分子，和 可能是核基质 我们的假设是， 在supB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 supB细胞的生长和基因表达直接 与这些结构扰动有关。 细胞结构的改变， 锚定非依赖性生长，以及相关基因表达模式 这些细胞中肿瘤抑制表型的丧失可能是 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.