Ko Y, Koli K M, Banerji S S, Li W, Zborowska E, Willson J K, Brattain M G, Arteaga C L
Department of Biochemistry and Molecular Biology, Medical College of Ohio, P.O. Box 10008, Toledo, OH 43699-0008, USA.
Int J Oncol. 1998 Jan;12(1):87-94. doi: 10.3892/ijo.12.1.87.
The role of transforming growth factor (TGF)-beta type II receptor (T beta RII) in TGF-beta resistance and tumor progression is now well recognized. To test the effects of T beta RII loss in determining malignancy, we transfected a T beta RII-expressing, TGF-beta-sensitive, MCF-7 cell strain (ME24) with a tetracycline-repressible truncated T beta RII (kdT beta RII) construct lacking the cytoplasmic domain of the receptor. Transfection of kdT beta RII into parental ME24 cells (designated ME24t6 after transfection) resulted in high expression levels of kdT beta RII mRNA and cell surface protein which were reversible by tetracycline treatment. ME24t6 cells did not respond to exogenous TGF-beta 1 as measured by inhibition of proliferation or fibronectin (FN) induction, indicating that the truncated T beta RII acted as a dominant-negative inhibitor of both the growth inhibitory and extracellular matrix (ECM) stimulatory TGF-beta effects. Furthermore, inhibition of kdT beta RII expression by tetracycline treatment led to TGF-beta 1-mediated cell growth arrest in the G1 phase of cell cycle and to the accumulation of the hypophosphorylated form of retinoblastoma (Rb) protein. However, compared to parental ME24 cells, transfectants failed to show increased tumorigenicity, indicating that loss of T beta RII itself is not sufficient to account for differences in the malignant properties of T beta RII-expressing and non-expressing MCF-7 cell strains.
转化生长因子（TGF）-βⅡ型受体（TβRII）在TGF-β抵抗和肿瘤进展中的作用现已得到充分认识。为了测试TβRII缺失对确定恶性肿瘤的影响，我们用一种缺乏受体胞质结构域的四环素可抑制性截短TβRII（kdTβRII）构建体转染了表达TβRII、对TGF-β敏感的MCF-7细胞系（ME24）。将kdTβRII转染到亲代ME24细胞中（转染后命名为ME24t6），导致kdTβRII mRNA和细胞表面蛋白的高表达水平，而四环素处理可使其逆转。通过抑制增殖或诱导纤连蛋白（FN）来检测，ME24t6细胞对外源性TGF-β1无反应，这表明截短的TβRII作为生长抑制和细胞外基质（ECM）刺激的TGF-β效应的显性负性抑制剂。此外，四环素处理抑制kdTβRII表达导致TGF-β1介导的细胞在细胞周期的G1期生长停滞，并导致视网膜母细胞瘤（Rb）蛋白低磷酸化形式的积累。然而，与亲代ME24细胞相比，转染子并未显示出更高的致瘤性，这表明TβRII本身的缺失不足以解释表达TβRII和不表达TβRII的MCF-7细胞系在恶性特性上的差异。
