Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1997-03-10
1999-03-30
Huff, Sheela
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 6, 435 77, 435 79, 435 791, 435 792, 435 793, 435 794, 435 795, 435 405, 435960, G01N 3353
Patent
active
058887466
DESCRIPTION:
BRIEF SUMMARY
The invention relates to the diagnosis and prognosis of cancers, particularly colorectal carcinomas.
The tumorigenic process leading to colorectal carcinoma formation involves multiple genetic alterations (Fearon et al (1990) Cell 61, 759-767). Tumor suppressor genes such as p53, DCC and APC are frequently inactivated in colorectal carcinomas, typically by a combination of genetic deletion of one allele and point mutation of the second allele (Baker et al (1989) Science 244, 217-221; Fearon et al (1990) Science 247, 49-56; Nishisho et al (1991) Science 253, 665-669; and Groden et al (1991) Cell 66, 589-600). Recently, mutation of two mismatch repair genes which regulate genetic stability was associated with a form of familial colon cancer (Fishel et al (1993) Cell 75, 1027-1038; Leach et al (1993) Cell 75, 1215-1225; Papadopoulos et al (1994) Science 263, 1625-1629; and Bronner et al (1994) Nature 368, 258-261). Proto-oncogenes such as myc and ras are altered in colorectal carcinomas, with c-myc RNA being overexpressed in as many as 65% of carcinomas (Erisman et al (1985) Mol. Cell. Biol. 5, 1969-1976), and ras activation by point mutation occurring in as many as 50% of carcinomas (Bos et al (1987) Nature 327, 293-297; and Forrester et al (1987) Nature 327, 298-303). Other proto-oncogenes, such as myb and neu are activated with a much lower frequency (Alitalo et al (1984) Proc. Natl. Acad. Sci. USA 81, 4534-4538; and D'Emilia et al (1989) Oncogene 4, 1233-1239). No common series of genetic alterations is found in all colorectal tumors, suggesting that a variety of such combinations may be able to generate these tumors.
Increased tyrosine phosphorylation is a common element in signalling pathways which control cell proliferation. The deregulation of protein tyrosine kinases (PTKS) through overexpression or mutation has been recognized as an important step in cell transformation and tumorigenesis, and many oncogenes encode PTKs (Hunter (1989) in oncogenes and the Molecular Origins of Cancer, ed. Weinberg (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.), pp. 147-173). Numerous studies have addressed the involvement of PTKs in human tumorigenesis. Activated PTKs associated with colorectal carcinoma include c-neu (amplification), trk (rearrangement), and c-src and c-yes (mechanism unknown) (D'Emilia et al (1989), ibid; Martin-Zanca et al (1986) Nature 3, 743-748; Bolen et al (1987) Proc. Natl. Acad. Sci. USA 84, 2251-2255; Cartwright et al (1989) J. Clin. Invest. 83, 2025-2033; Cartwright et al (1990) Proc. Natl. Acad. Sci. USA 87, 558-562; Talamonti et al (1993) J. Clin. Invest. 91, 53-60; and Park et al (1993) Oncogene 8, 2627-2635).
Obviously, protein tyrosine phosphatases (PTPs) are also intimately involved in regulating cellular phosphotyrosine levels. The growing family of PTPs consists of non-receptor and receptor-like enzymes (for review see Charbonneau et al (1992) Annu. Rev. Cell. Biol. 8, 463-493; and Pot et al (1992) Biochim. Biophys. Acta 1136, 35-43). All share a conserved catalytic domain, which in the non-receptor PTPs is often associated with proximal or distal sequences containing regulatory elements directing protein-protein interaction, intracellular localization, or PTP stability. The receptor like PTPs usually contain two catalytic domains in their intracellular region, and in addition have a transmembrane region and heterogeneous extracellular regions. The extreme diversity of the extracellular region, compared to the relatively conserved intracellular portion of these enzymes, suggests that these PTPs are regulated by specific extracellular factors, few of which have been identified. Some PTPs can act in opposition to PTKS. For example, the nonreceptor PTP 1B and TC-PTP can reverse or block cell transformation induced by the oncogenic tyrosine kinases neu or v-fms, while another non-receptor PTP (known as 3HC134, CL100, HVH1, PAC-1, erp, or MKP-1) can reverse the PTK-mediated activation of a central signalling enzyme, MAP kinase (Brown-Shimer et al (1992) Cancer Res. 52, 4
REFERENCES:
patent: 5538886 (1996-07-01), Schlessinger et al.
Seminars in Cell Biology, vol. 4, 1993 pp. 403-408, C.J. Pallen "The receptor-like protein tyrosine phsphatase alpha: a role in cell proliferation and oncogenesis".
The Journal of Biological Chemistry, vol. 269, No. 3, 21 Jan. 1994 pp. 2075-2081, T. Matozaki et al., "Molecular cloning of a human transmembrane-type protein tyrosine phosphatase and its expression in gastrointestinal cancers".
Cancer Letters, vol. 93, No. 2, 13 Jul. 1995 pp. 239-248, K. Tabiti et al., "Increased mRNA expression of the receptor-like protein tyrosine phosphatase alpha in late stage colon carcinomas".
Letters to Nature, vol. 346, 23 Aug. 1990, pp. 756-760, A.C. Schuh et al., "obligatory wounding requirement for tumorigenesis in v-jun transgenic mice".
Pallen Catherine Jane
Tabiti Karim
Huff Sheela
Institute of Molecular and Cell Biology
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