Mouse platelet-derived growth factor alpha receptor: sequence, tissue-specific expression and correlation with...

Area of Science:

• Molecular Biology
• Oncology
• Genetics

Background:

• Proto-oncogenes can encode cell-surface receptors for growth factors.
• Metastasis involves the spread of cancer cells from the primary tumor.
• Differential gene expression is crucial in cancer progression.

Purpose of the Study:

• To identify proto-oncogenes differentially expressed in high-metastatic versus low-metastatic murine tumor cells.
• To investigate the role of these genes in cancer metastasis.

Main Methods:

• Screening of metastatic murine tumor cells for differential proto-oncogene expression.
• Cloning and sequence analysis of a specific mRNA transcript.
• Northern blot analysis and immunoprecipitation assays.

Main Results:

• A 6.5-kb mRNA, identified as the murine platelet-derived growth factor alpha (PDGF-alpha) receptor, was expressed in high-metastatic clones (3LL carcinoma, T10 sarcoma) but not low-metastatic clones.
• The murine PDGF-alpha receptor cDNA predicts a 1089 amino acid protein with high sequence identity to human and rat counterparts.
• The PDGF-alpha receptor gene was preferentially expressed in high-metastatic clones and specific normal mouse tissues.
• 185-kDa and 170-kDa proteins were specifically precipitated from high-metastatic D122 cells, but not low-metastatic A9 cells.

Conclusions:

• The murine homolog of the platelet-derived growth factor alpha (PDGF-alpha) receptor is preferentially expressed in high-metastatic tumor cell clones.
• Overexpression of the PDGF-alpha receptor in highly metastatic clones may contribute to increased lung metastasis capacity.