Inhibitory effects of a luteinizing hormone-releasing hormone agonist on basal and epidermal growth factor-induced cell proliferation and metastasis-associated properties in human epidermoid carcinoma A431 cells
| Autor: | Ming Ting Lee, Jiuan Jiuan Hwang, Lung Ta Lee, Ping Ping H. Lee, Tung Bin Lo, Ying Tang Huang, Ferng Chun Ke, Charles Liebow, Andrew V. Schally |
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| Rok vydání: | 2002 |
| Předmět: |
Threonine
endocrine system Cancer Research medicine.medical_specialty Time Factors Antineoplastic Agents Hormonal medicine.medical_treatment Immunoblotting Protein tyrosine phosphatase DNA Fragmentation Biology Cell morphology Gonadotropin-Releasing Hormone chemistry.chemical_compound Epidermal growth factor Internal medicine medicine Serine Tumor Cells Cultured Humans Neoplasm Invasiveness Kinase activity Phosphorylation Triptorelin Pamoate Epidermal Growth Factor Growth factor Tyrosine phosphorylation Precipitin Tests Matrix Metalloproteinases Enzyme Activation Endocrinology Oncology Epidermoid carcinoma chemistry Caspases Carcinoma Squamous Cell Protein Tyrosine Phosphatases A431 cells hormones hormone substitutes and hormone antagonists Cell Division |
| Zdroj: | International journal of cancer. 99(4) |
| ISSN: | 0020-7136 |
| Popis: | The purpose of this study was to investigate the effects of a potent LHRH agonist, [D-Trp(6)]LHRH on the basal and EGF-induced cell proliferation and the metastasis-associated properties in A431 human epidermoid carcinoma. [D-Trp(6)]LHRH time-dependently inhibited the basal and EGF-stimulated growth of A431 cancer cells. It is assumed that phosphorylation/dephosphorylation of cellular proteins is highly related to cell growth. This study demonstrates that [D-Trp(6)]LHRH decreased the basal and EGF-induced total cellular kinase activity, particularly the tyrosine phosphorylation of several cellular proteins including the EGFR. In contrast, [D-Trp(6)]LHRH did not cause detectable changes in basal and EGF-stimulated serine/threonine phosphorylation of A431 cellular proteins. The inhibitory effect of [D-Trp(6)]LHRH on A431 cell proliferation was associated with apoptosis as evidenced by the cell morphology and DNA integrity (ladder pattern), the expression of interleukin 1beta-converting enzyme (ICE) and activation of caspase. Furthermore, EGF could rescue the remaining attached A431 cells following [D-Trp(6)]LHRH treatment for 48 hr, which suggests that limited exposure to [D-Trp(6)]LHRH did not channel all cells to irreversible apoptotic process. We also determined the effects of [D-Trp(6)]LHRH on metastasis-associated properties in A431 cells. [D-Trp(6)]LHRH reduced both basal and EGF-stimulated secretion of MMP-9 and MMP-2. In addition, [D-Trp(6)]LHRH suppressed the basal and EGF-induced invasive activity of A431 cells based on an in vitro invasion assay. In conclusion, this study indicates that [D-Trp(6)]LHRH may act partly through activating tyrosine phosphatase activity to inhibit cell proliferation and the metastasis-associated properties of A431 cancer cells. Our work suggests that [D-Trp(6)]LHRH may be therapeutically useful in limiting the tumor growth and metastasis of some neoplasms. |
| Databáze: | OpenAIRE |
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