Grundy P, Bishayee S, Disa S, Scher C D
Division of Oncology, Children's Hospital of Philadelphia, Pennsylvania.
Cancer Res. 1989 Jul 1;49(13):3581-6.
BP3T3, a clonal benzo(a)pyrene-transformed BALB/c-3T3 cell, has been shown to be conditionally responsive to platelet-derived growth factor (PDGF)-stimulated DNA synthesis. PDGF stimulates DNA synthesis in BP3T3 cell cultures maintained in 0.5% platelet-poor plasma, but pretreatment with 10% serum or 10 micrograms/ml insulin inhibits PDGF-modulated DNA synthesis. BALB/c-3T3 cells remain mitogenically responsive irrespective of pretreatment with serum or insulin. The present study demonstrates that pretreatment with serum or insulin inhibits BP3T3 cell DNA synthesis by affecting receptor function. Insulin and serum, however, act through different mechanisms. Pretreatment with serum for 3 or more days down-modulated the BP3T3 cell PDGF receptor, resulting in both inhibition of PDGF binding and inhibition of PDGF-stimulated receptor autophosphorylation. In contrast, treatment of nontransformed BALB/c-3T3 cells with serum for 3 or more days did not down-modulate the PDGF receptor. Pretreatment of BP3T3 cells with insulin did not inhibit PDGF binding to BP3T3 cells but did inhibit PDGF-stimulatable tyrosine-specific receptor autophosphorylation. This effect was minimal to nonexistent in BALB/c-3T3 cell cultures. It appears likely that pretreatment of BP3T3 cells with insulin either inhibits the tyrosine kinase activity of the PDGF receptor or activates receptor dephosphorylation.
BP3T3是一种经苯并(a)芘转化的克隆BALB/c - 3T3细胞，已被证明对血小板衍生生长因子(PDGF)刺激的DNA合成具有条件性反应。PDGF可刺激在0.5%贫血小板血浆中培养的BP3T3细胞的DNA合成，但用10%血清或10微克/毫升胰岛素预处理可抑制PDGF调节的DNA合成。无论是否用血清或胰岛素预处理，BALB/c - 3T3细胞仍保持有丝分裂反应性。本研究表明，血清或胰岛素预处理通过影响受体功能来抑制BP3T3细胞的DNA合成。然而，胰岛素和血清的作用机制不同。用血清预处理3天或更长时间可下调BP3T3细胞的PDGF受体，导致PDGF结合受抑制以及PDGF刺激的受体自身磷酸化受抑制。相比之下，用血清处理未转化的BALB/c - 3T3细胞3天或更长时间并不会下调PDGF受体。用胰岛素预处理BP3T3细胞不会抑制PDGF与BP3T3细胞的结合，但会抑制PDGF可刺激的酪氨酸特异性受体自身磷酸化。这种效应在BALB/c - 3T3细胞培养物中极小或不存在。BP3T3细胞用胰岛素预处理似乎可能会抑制PDGF受体的酪氨酸激酶活性或激活受体去磷酸化。
