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Markers in breast cancer

Endothelial cell growth factor,
platelet-derived
(PD-ECGF)



Other name(s)

Endothelial cell growth factor 1 (ECGF1)
Thymidine phosphorylase (TP)
Gliostatin
ECGF1 (gene locus)


Molecular biology

Gene: ECGF1 maps to 22q13.32-qter (Stenman G. et al., 1992). It contains 10 exons spanning more than 4.3 kb. Its promoter lacks a TATA box and a CCAAT box, structures characteristic of eukaryotic promoters. Instead, six copies of potential Sp1-binding sites (GGGCGG or CCGCCC) are clustered just upstream of the transcription start sites. (Hagiwara K. et al., 1991).
mRNA: size: 1.8 kb. In addition to this mRNA, the human epidermoid carcinoma cell line A431 was found to express 3.0 kb and 3.2 kb transcripts. cDNA cloning of the larger transcripts revealed that they contain long 5' leader sequences of 1.5 kb and 1.7 kb, respectively, and the same open reading frame encoding PD-ECGF/TP as that of the 1.8 kb transcript (Usuki K. et al., 1994).
Protein: a 90-kDa protein consisting of two non-covalently associated subunits. PD-ECGF is an angiogenic factor distinct from the endothelial cell mitogens of the fibroblast growth factor family. PD-ECGF, which is stored in platelets as a 45-kD single polypeptide chain, has a highly restricted target cell specificity acting only on endothelial cells. It promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells.


Breast cancer

Cell lines:

Tumors:
- Ribonuclease protection assays and immunohistochemistry were used to examine the expression of PD-ECGF in 240 primary breast carcinomas. Nuclear and/or cytoplasmic PD-ECGF expression was observed in the neoplastic tumour epithelium in 53% of tumours. Immunoreactivity was also often present in the stromal, inflammatory and endothelial cell elements. Although endothelial cell staining was usually focal, immunoreactivity was observed in 61% of tumours and was prominent at the tumour periphery, an area where tumour angiogenesis is most active. Tumour cell PD-ECGF expression was significantly inversely correlated with grade and size but no association was observed with other tumour variables. Relapse-free survival was higher in node-positive patients with elevated PD-ECGF but not in other patient groups. This might be due to the potentiation of chemotherapeutic agents like methotrexate by PD-ECGF (Fox S.B. et al., 1996).

- Using immunohistochemical methods, PD-ECGF expression and vascularity have been studied in DCIS (n = 34) and invasive carcinoma (n = 32). Stromal vascularity in DCIS was associated with PD-ECGF expression in the perivascular inflammatory cells and in the cytoplasm of carcinoma cells. In invasive carcinoma, no relationship was found between vascularity and PD-ECGF expression in either the carcinoma or the inflammatory cells (Lee A.H. et al., 1999).


References

Fox S.B. et al. (1996) The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium. Br. J. Cancer 73, 275-280. (PubMed)
Hagiwara K. et al. (1991) Organization and chromosomal localization of the human platelet-derived endothelial cell growth factor gene. Molec. Cell. Biol. 11, 2125-2132. (PubMed)
Lee A.H. et al. (1999) Angiogenesis and expression of thymidine phosphorylase by inflammatory and carcinoma cells in ductal carcinoma in situ of the breast. J. Pathol. 187, 285-290. (PubMed)
Stenman G. et al. (1992) Regional localization of the human platelet-derived endothelial cell growth factor (ECGF1) gene to chromosome 22q13. Cytogenet. Cell Genet. 59, 22-23. (PubMed)
Usuki K. et al. (1994) Structural properties of 3.0 kb and 3.2 kb transcripts encoding platelet-derived endothelial cell growth factor/thymidine phosphorylase in A431 cells. Biochim. Biophys. Acta 1222, 411-414. (PubMed)


See also

UniGene data (Hs.73946)



Latest modification of this page

September 2000



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