Subtraction hybridization identifies a melanoma differentiation associated gene (mda-7) with elevated expression in growth arrested and terminally differentiated human melanoma cells.
This scheme identified melanoma differentiation associated gene-7 (mda-7), whose expression is up-regulated as a consequence of terminal differentiation in human melanoma cells.
To evaluate the mechanism underlying the differential expression of mda-7 as a function of melanoma progression and induction of growth arrest and differentiation in human melanoma cells the promoter region of this gene has been isolated from a human placental genomic library and characterized.
The melanoma differentiation-associated gene-7 (mda-7), cloned from a human melanoma cell line H0-1, is known to induce tumor cell-selective growth inhibition in breast cancer cells in vitro and loss of tumorigenicity ex vivo.
Through subtraction hybridization, we have identified a gene associated with induction of irreversible growth arrest, cancer reversion, and terminal differentiation in human melanoma cells, melanoma differentiation associated gene-7 (mda-7).
However, in keeping with a possible role as a tumor suppressor, MDA-7 expression is decreased in more advanced melanomas, with nearly undetectable levels in metastatic disease.
De novo mda-7 mRNA expression is also detected in human melanocytes and expression is inducible in cells of melanocyte/melanoma lineage and in certain normal and cancer cell types following treatment with a combination of IFN-beta plus MEZ.
When expressed by means of a replication incompetent adenovirus (Ad.mda-7) growth of melanoma, but not normal early passage or immortal human melanocytes, is dramatically suppressed and cells undergo programmed cell death (apoptosis).
Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via up-regulation of the double-stranded RNA-dependent protein kinase (PKR).
Subtraction hybridization identified melanoma differentiation-associated gene-7 (mda-7) as a gene induced during terminal differentiation in human melanoma cells.
Subtraction hybridization between terminally differentiated and untreated melanoma cells identified melanoma differentiation-associated gene-7 (mda-7), which is selectively induced during the process of melanoma terminal differentiation.
The melanoma differentiation-associated gene-7 (mda-7) was cloned by subtraction hybridization as a molecule whose expression is elevated in terminally differentiated human melanoma cells.
In vitro studies revealed that iNOS expression in melanoma cell lines is lost in a dose-dependent fashion after treatment with an adenoviral vector encoding the mda-7 gene (Ad-mda7) or with rhMDA-7 protein, demonstrating that MDA-7 down-regulates iNOS expression.
In vitro studies revealed that iNOS expression in melanoma cell lines is lost in a dose-dependent fashion after treatment with an adenoviral vector encoding the mda-7 gene (Ad-mda7) or with rhMDA-7 protein, demonstrating that MDA-7 down-regulates iNOS expression.
Subtraction hybridization identified melanoma differentiation associated gene-7 (mda-7) as a gene associated with melanoma cell growth, differentiation and progression.
Subtraction hybridization identified melanoma differentiation associated gene-7 (mda-7) as a gene associated with melanoma cell growth, differentiation and progression.
Strategies designed to replace this defective tumor suppressor protein, as well as forced expression of a novel cancer specific apoptosis inducing gene, melanoma differentiation associated gene-7 (mda-7), offer promise for restoring apoptosis in tumor cells.
Melanoma differentiation-associated 7 (mda-7) (interleukin 24), when expressed via a recombinant replication-defective adenovirus, adenovirus (Ad).mda-7, has profound antiproliferative and cytotoxic effects in a variety of tumor cells but not in nontransformed cells.