Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Cyclic peptides
Patent
1994-10-27
1999-02-23
Achutamurthy, Ponnathapura
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
Cyclic peptides
530328, 514 11, 514 9, 514 8, C07K 752, C07K 700
Patent
active
058745289
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to the field of blocking peptides which interact with ligand growth factor receptors. Specifically, the blocking peptides of the invention are capable of binding to ligands to the epidermal growth factor receptor and the erbB-2 receptor. The present invention further relates to the use of such blocking peptides in assays to detect the presence of ligand growth factors. Methods of using the blocking peptides of the invention as a means of inhibiting the growth of adenocarcinoma cells and for diagnosing cancer are also disclosed.
2. Review of Related Art
Transforming growth factor ligands belong to a family of heat and acid-stable polypeptides which allow cells to assume a transformed morphology and form progressively growing colonies in anchorage-independent growth assays (DeLarco, et al., Proc. Natl. Acad. Sci. USA, 75:4001-4005 (1978); Moses, et al., Cancer Res., 41:2842-2848 (1981); Ozanne, et al., J. Cell. Physiol., 105:163-180 (1980); Roberts, et al., Proc. Natl. Acad. Sci. USA, 77:3494-3498 (1980)). The epidermal growth factor receptor (EGFR) and its physiologic ligands, epidermal growth factor (EGF) and transforming growth factor alpha (TGF.alpha.), play a prominent role in the growth regulation of many normal and malignant cell types (Carpenter, G., Annu. Rev. Biochem., 5:881-914 (1987)).
One role the EGF receptor system may play in the oncogenic growth of cells is through autocrine-stimulated growth. If cells express the EGFR and secrete EGF and/or TGF.alpha. then such cells could stimulate their own growth. Since some human breast cancer cell lines and tumors express EGFR (Osborne, et al., J. Clin. Endo. Metab., 55:86-93 (1982); Fitzpatrick, et al., Cancer Res., 44:3442-3447 (1984); Filmus, et al., Biochem. Biophys. Res. Commun., 128:898-905 (1985); Davidson, et al., Mol. Endocrinol., 1:216-223 (1987); Sainsbury, et al., Lancet, i: 1398-1402 (1987); Perez, et al., Cancer Res. Treat., 4:189-193 (1984)) and secrete TGF.alpha. A (Bates, et al., Cancer Res., 46:1707-1713 (1986); Bates, et al., Mol. Endocrinol., 2:543-555 (1988)), an autocrine growth stimulatory pathway has been proposed in breast cancer (Lippman, et al., Breast Cancer Res. Treat., 7:59-70 (1986)).
An autocrine growth stimulatory pathway analogous to that proposed for epidermal growth factor receptor and its ligands may also be employed by a growing list of oncogene encoded transmembrane proteins that have structure reminiscent of growth factor receptors. This list includes the protooncogenes neu and its human equivalent erbB-2 or HER2 (Bargmann, et al., Nature, 319:226-229 (1986); Coussens, et al., Science, 230:1131-1139 (1985); Yamamoto, et al., Nature, 319:230-234 (1986); c-kit (Yarden, et al., EMBO J., 6:341-3351 (1987); ros (Neckameyer, et al., Mol Cell. Biol., 6:1478-1486 (1986); met (Park, et al., Proc. Natl. Acad. Sci. USA, 84:6379-6383 (1987); trk (Martin-Zanca, et al., Nature, 319:743-748 (1986); and ret (Takahashi, et al., Mol. Cell. Biol., 7:1378-1385 (1987)). The erbB-2 and c-kit protooncogenes encode factors that display structural homology with EGFR (Yarden, et al., Annu. Rev. Biochem., 57:443-478 (1988). Although erbB-2 and its related oncogene neu are related to EGFR, these proteins are distinct. For example, known EGFR ligands such as EGF and TGF.alpha. do not bind to erbB-2 receptor. (King, et al., EMBO J., 7:1647 (1988); and Stern, et al., EMBO J., 7:995 (1988).
Amplification or overexpression or both have been described for the c-erbB-2 gene in a number of human adenomas (Semba, et al., Proc. Natl. Acad. Sci. USA, 82:6497 (1985); Van de Vijver, et al., Mol. Cell. Biol., 7:2019 (1987); Yokota, et al., Oncogene, 2:283 (1988); Slamon,et al., Science 244:707 (1989); Aasland, et al., Br. J. Cancer, 57:358 (1991); Cline, et al., Cancer, 60:2669 (1991)). Overexpression statistically correlates with short term relapse in breast (Slamon, et al., Science, 235:177 (1987); Walker, et al., Br. J. Cancer, 60:426 (1991); Wright, et at., Cancer Res., 49:2
REFERENCES:
patent: 4933294 (1990-06-01), Waterfield et al.
patent: 5030565 (1991-07-01), Niman et al.
patent: 5367060 (1994-11-01), Vandlen et al.
Yamamoto et al, Nature, vol. 319, pp. 230-234, (Jan. 16, 1986).
Lippman Marc E.
Lupu Ruth
Achutamurthy Ponnathapura
Georgetown University
Wessendorf T. D.
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