Tatzel, Jutta and Poser, Ina and Schroeder, Josef and Bosserhoff, Anja K. (2005) Inhibition of melanoma inhibitory activity (MIA) expression in melanoma cells leads to molecular and phenotypic changes. PIGMENT CELL RESEARCH, 18 (2). pp. 92-101. ISSN 0893-5785,
Full text not available from this repository. (Request a copy)Abstract
The secreted protein melanoma inhibitory activity (MIA) is highly expressed in malignant melanoma but not in melanocytes and is associated with tumor progression in vivo. Here, we further investigated the functional role of MIA by inhibiting MIA expression of the human melanoma cell line HMB2 via stable antisense MIA cDNA transfection, and subsequent analysis of the cell clones. MIA-deficient cell clones showed several changes in cell morphology and growth pattern. In monolayer and three-dimensional culture enhanced cell-cell contacts were formed. Furthermore, a re-induction of pigment synthesis in comparison with the amelanotic parental cell line HMB2 was observed. Molecular analyses revealed a re-expression of tyrosinase-related protein 1 (Trp-1) and tyrosinase in the MIA-deficient cell clones necessary for melanin synthesis. In accordance, re-expression of MIA in the MIA-deficient melanoma cell clones resulted in downregulation of Trp-1. To identify the molecular mechanisms of MIA regulating pigmentation, MITF and PAX3, two positive regulators of Trp-1 and tyrosinase transcription, and PIAS3, a negative regulator of MITF activity, were analyzed. Only in MIA-deficient cells, expression of PAX3 mRNA and MITF protein was found. In contrast, strong expression of PIAS3 was detected in HMB2 but not in the MIA-deficient cells. To our knowledge this is the first report demonstrating a correlation between MIA expression and pigmentation and morphology of melanocytic cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MICROPHTHALMIA TRANSCRIPTION FACTOR; MALIGNANT-MELANOMA; FUNCTIONAL-ROLE; PROTEIN-1 TRP1; FACTOR TBX2; IN-VITRO; GENE; TYROSINASE; ACTIVATION; PIGMENTATION; melanoma; melanoma inhibitory activity; pigmentation; tyrosinase; Trp-1; MITF |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 May 2021 08:43 |
| Last Modified: | 18 May 2021 08:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36337 |
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