epidermal-growth-factor and Rhabdoid-Tumor

To investigate the effects of the autocrine loop of epidermal growth factor receptor (EGFR)-epidermal growth factor (EGF) / transforming growth factor-alpha (TGF-alpha) on the proliferation and differentiation of malignant rhabdoid tumor (MRT), we used five MRT cell lines, TM87-16, STM91-01, TTC549, TTC642, and YAM-RTK1. RT-PCR analyses revealed expression of EGFR mRNA in all MRT cell lines. In contrast, the expression of either EGF or TGF-alpha mRNA was detected in all MRT cell lines. Expression of EGF, TGF-alpha, and EGFR as determined by immunocytochemical staining and in situ hybridization, correlated with the results of RT-PCR. Upon differentiation-induction with 12-O-tetradecanoylphorbol-13-acetate (TPA), in TTC549, showing an expression of TGF-alpha but not EGF initially, de novo expression of EGF mRNA appeared abruptly on day 2 of TPA treatment. To confirm the EGFR-EGF / TGF-alpha autocrine loop, we used TGF-alpha, EGF, and their antibodies in the cultures. Monoclonal antibody (mAb) to EGFR alone significantly inhibited the growth of cell line TTC549. However, mAb to EGF or TGF-alpha could inhibit proliferation of this cell line only when administrated together. Our findings would suggest that growth of the TTC549 cell line is constitutionally regulated by TGF-alpha / EGFR, but that inhibition of this autocrine mechanism results in transient activation of an autocrine loop involving EGF / EGFR. Our results may indicate the presence of two different autocrine loops of EGFR-EGF and / or EGFR-TGF-alpha in MRT cell lines. The heterogeneity of autocrine mechanisms found in MRT cell lines would be consistent with the multiphenotypic diversity and aggressive characteristics of this enigmatic tumor.

Topics: Adult; Antibodies, Monoclonal; Cell Differentiation; Cell Division; Cell Line; Child; Epidermal Growth Factor; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Humans; In Situ Hybridization; Male; Reverse Transcriptase Polymerase Chain Reaction; Rhabdoid Tumor; RNA, Messenger; Tetradecanoylphorbol Acetate; Transcription, Genetic; Transforming Growth Factor alpha; Tumor Cells, Cultured