Finzi E, Fleming T, Pierce J H
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland.
J Invest Dermatol. 1990 Oct;95(4):382-7. doi: 10.1111/1523-1747.ep12555464.
Transforming growth factor alpha (TGF alpha) is a peptide so named because it helps to impart anchorage-independent growth to normal rat kidney (NRK) cells in vitro and is secreted by many rodent and human tumor cells. To directly investigate the transforming properties of this factor, we constructed a replication-defective murine retrovirus that expresses the human sequence coding for TGF alpha. Infection of NIH/3T3 cells with the TGF alpha retrovirus led to the integration of a transcriptionally active provirus and overexpression of biologically active TGF alpha, but failed to induce morphologic transformation. Similarly, the TGF alpha retrovirus failed to induce morphologic transformation of five other types of rodent fibroblasts. We also investigated the effect of TGF alpha expression on the growth of BALB/MK mouse keratinocytes, which require epidermal growth factor (EGF) for proliferation. We show that exogenously added TGF alpha is an extremely potent mitogen for BALB/MK cells. However, retroviral expression of TGF alpha in BALB/MK cells failed to relieve dependence on exogenously added EGF (or TGF alpha) for cell growth. These results suggest that overexpression of TGF alpha does not, by itself, transform rodent fibroblasts or keratinocytes.
转化生长因子α（TGFα）是一种肽，之所以这样命名，是因为它有助于使正常大鼠肾（NRK）细胞在体外获得不依赖贴壁的生长能力，并且由许多啮齿动物和人类肿瘤细胞分泌。为了直接研究该因子的转化特性，我们构建了一种复制缺陷型鼠逆转录病毒，它表达编码TGFα的人类序列。用TGFα逆转录病毒感染NIH/3T3细胞导致转录活性前病毒的整合以及生物活性TGFα的过表达，但未能诱导形态转化。同样，TGFα逆转录病毒未能诱导其他五种类型的啮齿动物成纤维细胞发生形态转化。我们还研究了TGFα表达对BALB/MK小鼠角质形成细胞生长的影响，该细胞增殖需要表皮生长因子（EGF）。我们发现，外源添加的TGFα是BALB/MK细胞极强的促有丝分裂原。然而，TGFα在BALB/MK细胞中的逆转录病毒表达未能消除细胞生长对外源添加的EGF（或TGFα）的依赖。这些结果表明，TGFα的过表达本身并不能转化啮齿动物成纤维细胞或角质形成细胞。
