Biomedical subjects

C Fitzer-Attas

Publications and source records attributed to C Fitzer-Attas.

3 recordsLinked to original sources

PubMed1994

The expression of PDGF-alpha but not PDGF-beta receptors is suppressed in Swiss/3T3 fibroblasts over-expressing protein kinase C-alpha.

The generation and characterization of Swiss/3T3 cells which stably over-express protein kinase C (PKC)-alpha were previously described by us. In these cells over-expression of PKC-alpha reduced the expression of epidermal growth factor (EGF) receptor molecules [(1990) J. Biol. Chem. 265, 13290-13296]. Here we show that the expression of PDGF-alpha receptors, but not PDGF-beta receptors, was specifically decreased in these cells. Not only were the levels of PDGF-alpha receptor mRNA transcript and protein significantly diminished in the PKC-alpha over-producing cells, but their ability to respond to short- and long-term growth factor signals was appropriately compromised. This was reflected in a reduced tyrosine autophosphorylation signal in response to PDGF-AA, as well as in decreased growth rates of PKC-alpha over-expressing cells when supplied with external PDGF-AA. A similar decrease in PDGF-alpha receptors was also demonstrated in parental Swiss/3T3 cells treated with phorbol esters. Our studies imply that PKC-alpha is involved in a cellular mechanism suppressing the expression of PDGF-alpha receptors in Swiss/3T3 cells. Hence, activation of PKC-alpha or alterations in its cellular levels may affect, in turn, the expression of a specific set of cell surface receptors and their responses to external growth factors.

3T3 Cells↗

PubMed1993

Expression of functionally intact PDGF-alpha receptors in highly metastatic 3LL Lewis lung carcinoma cells.

The ability of disseminating tumor cells to grow in a target organ is the final limiting step of the metastatic cascade. The growth of a highly lung-metastatic clone, D122, of the murine 3LL Lewis lung carcinoma was induced in vitro with lung-conditioned media (CM) to a greater extent than that of a weakly metastatic clone, A9. With the use of platelet-derived growth factor (PDGF)-alpha-receptor-specific antibodies, the possible paracrine mode of metastatic cell growth was further suggested by demonstrating the presence of these receptors on highly metastatic cells only. Receptors for PDGF have been found almost exclusively on cells of mesenchymal and glial origin. Therefore, the functionality of this receptor in the D122 epithelial cell line was verified by immune complex kinase and ligand-stimulation assays. Moreover, PDGF was shown to specifically induce in vitro growth of D122 highly metastatic cells only and to be abundantly expressed in lung CM but not in kidney or liver CM. Thus, the interaction of PDGF-like factors in the lung with PDGF receptors on the metastatic tumor cell may be important in the development of metastatic lesions in the target organ.

Amino Acid Sequence↗

PubMed1992

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

High- and low-metastatic cells derived from metastatic murine tumors were screened for the differential expression of proto-oncogenes which may code for cell-surface receptors to growth factors. We found that metastatic clones of 3LL carcinoma and T10 sarcoma but not non-metastatic clones of these tumors express a 6.5-kb mRNA that is recognized by a v-fms probe containing a tyrosine kinase domain. The cloning and sequence analysis of a full-length cDNA clone corresponding to the v-fms-related 6.5-kb transcript showed that this transcript is the murine homolog of platelet-derived growth factor alpha (PDGF-alpha) receptor. The cDNA contains an open reading frame that predicts a 1089 amino acid protein. Comparison with the human and rat PDGF-alpha receptor reveals an overall amino acid sequence identity of 91% and 94% respectively. Northern blot analysis shows that this gene is preferentially expressed in the high-metastatic clones and is also selectively expressed in normal mouse tissues. Immunoprecipitation using anti-PDGF-alpha receptor serum shows that 185-kDa and 170-kDa proteins were specifically precipitated from cells of the high-metastatic D122 but not from the low-metastatic A9 cells. The possibility that overexpression of PDGF-alpha receptor in high-metastatic clones may contribute to an increase in the capacity of tumor cells to generate metastases in the lung is discussed.

Amino Acid Sequence↗