RHoB as a suppressor of cancer cell growth, cell...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C435S006120, C435S455000, C435S069100, C435S456000, C435S325000, C435S366000

Reexamination Certificate

active

07135463

ABSTRACT:
The present invention concerns the use of the protein RhoB and its variants to inhibit cancer cell growth, migration, invasion, metastasis, malignant cell transformation, and/or to modulate oncogenic signaling, wherein introducing RhoB directly, or indirectly via a nucleic acid sequence encoding RhoB, into a malignantly transformed cell or a cancerous cell decreases phosphorylation of Erk and Akt proteins inhibiting the PI3-kinase/Akt cell survival pathway and promoting apoptotic cell death. In one aspect, the compositions and methods of the present invention are used to inhibit the malignant transformation of cells by the oncogenes H-Ras, N-Ras, K-Ras, EGFR, or ErbB2, or to inhibit the growth of cancer cells transformed by such oncogenes. The compositions and methods of the present invention may be used to inhibit cancer cell growth, inhibit malignant cell transformation, and modulate oncogenic signaling in vivo or in vitro.

REFERENCES:
patent: 2002/0034725 (2002-03-01), McKenna et al.
patent: 2003/0018003 (2003-01-01), Sebti
Pendergast and Rane, Farnesyltransferase inhibitors: mechanism and applications, Expert Opinion Invest Drugs, 2001, vol. 10 No. 12, pp. 2105-2116.
Adnane, J. et al. “Suppression of Rho B expression in invasive carcinoma from head and neck cancer patients”Clin Cancer Res, 2002, 8:2225-2232.
Alimandi, M. et al. “Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas”Oncogene, 1995, 10:1813-1821.
Arboleda, M.J. et al. “Overexpression of AKT2/protein kinase Bβ leads to up-regulation of β1 integrins, Increased invasion, and metastasis of human breast and ovarian cancer cells”Cancer Res, 2003, 63:196-206.
Buday, L. and Downward, J. “Epidermal growth factor regulates p21™ through the formation of a complex of receptor, Grb2 adaptor protein, and Sos nucleotide exchange factor”Cell, 1993, 73:611-620.
Chen, Z. et al. “Both famesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice”J Biol Chem, 2000, 275(24):17974-17978.
Davies, M.A. et al. “Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells”Clin Cancer Res, 2002, 8:1904-1914.
Du, W. and Prendergast, G.C. “Geranylgeranylated RhoB mediates suppression of human tumor cell growth by famesyltransferase Ihibitors”Cancer Res, 1999, 59:5492-5496.
Du, W. et al. “Cell growth inhibition by famesyltransferase inhibitors in mediated by gain of geranylgeranylated RhoB”Mol Cell Biol, 1999, 19(3):1831-1840.
Forget, M.A. et al. “The expression of Rho proteins decreased with human brain tumor progression: potential tumor markers”Clin Exp Metastasis, 2002, 19(1):9-15, abstract.
Fritz, G. and Kaina, B. “rhoB encoding a UV-inducible Ras-related small GTP-binding protein is regulated by GTPases of the Rho family and independent of JNK, ERK, and p38 MAP kinase”J Biol Chem, 1997, 272(49):30637-30644.
Fritz, G. et al. “The Ras-related small GTP-binding protein RhoB is immediate-early inducible by DNA damaging treatments”J Biol Chem, 1995, 270(42):25172-25177.
Hall, A. “Rho GTPases and the actin cytoskeleton”Science, 1998, 279(5350):509-514.
Hunter, T. “Oncoprotein networks”Cell, 1997, 88:333-346.
Jahner, D. and Hunter, T. “The ras-related gene rhoB is an immediate-early gene inducible by v-Fps, epidermal growth factor, and platelet-derived growth factor in rat fibroblasts”Mol Cell Biol, 1991, 11(7):3682-3690.
Jiang, K. Et al. “Regulation of Akt-dependent cell survival by Syk and Rac”Blood, 2003, 101:236-244.
Khosravi-Far, R. and Der, C.J. “The Ras signal transduction pathway”Cancer Metastasis Rev, 1994, 13:67-89.
Khosravi-Far, R. et al. “Activation of Rac1, RhoA, and mitogen-activated protein kinases Is required for Ras transformation”Mol Cell Biol, 1995, 15(11):6443-6453.
Kim, D. et al. “Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production”Faseb J, 2001, 15:1953-1962.
Kubiatowski, T. et al. “Association of increased phosphatidylinositol 3-kinase signaling with increased invasiveness and gelatinase activity in malignant gliomas”J Neurosurg, 2001, 95:480-488.
Lebowitz, P.F. et al. “Evidence that famesyltransferase inhibitors suppress Ras transformation by interfering with Rho activity”Mol Cell Biol, 1995, 15(12):6613-6622.
Lui, A. et al. “RhoB alteration is necessary for apoptotic and antineoplastic responses to famesyltransferase inhibitors”Mol Cell Biol, 2000, 20(16):6105-6113.
Liu, A. et al. “RhoB is required to mediate apoptosis in neoplastically transformed cells after DNA damage”Proc Natl Acad Sci USA, 2001, 98(11):6192-6197.
Luetteke, N.C. et al. “The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase”Genes Dev, 1994, 8:399-413.
Nakamura, T. et al. “Cloning of the RhoB gene from the mouse genome and characterization of its promoter region”Biochem. Biophys. Res. Commun., 1996, 226(3):688-694, abstract.
Park, B-K. et al. “Akt1 induces extracellular matrix invasion and matrix metalloproteinase-2 activity in mouse mammary epithelial cells”Cancer Res, 2001, 61:7647-7653.
Pruitt, K. and Der, C.J. “Ras and Rho regulation of the cell cycle and oncogenesis”Cancer Lett., 2001, 171(1):1-10.
Quilliam, L.A. et al. “Identification of residues critical for Ras(17N) growth-inhibitory phenotype and for Ras interaction with guanine nucleotide exchange factors”Mol Cell Biol, 1994, 14(2):1113-1121.
Stewart, A.L. et al. “P13K blockade by Ad-PTEN inhibits invasion and induces apoptosis in radial growth phase and metastatic metanoma cells”Mol Med, 2002, 8(8):451-461.
Symons, M. and Settleman, J. “Rho family GTPases: more than simple switches”Trends Cell Biol, 2000, 10(10):415-419.
Turkson, J. et al. “Requirement for Ras/Rac1-mediated p38 and c-Jun N-terminal kinase signaling in Stat3 transcriptional activity induced by the Src oncoprotein”Mol Cell Biol, 1999, 19(11):7519-7528.
Van Aelst, L. and D'Souza-Schorey, C. “Rho GTPases and signaling networks”Genes Dev, 1997, 11(18):2295-2322.
Vlahos, C.J. et al. “A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002)”J Biol Chem, 1994, 269(7):5241-5248.
Yano, H. et al. “Biochemical and pharmacological studies with KT7692 and LY294002 on the role of phosphatidylinositol 3-kinase in FcεRl-mediated signal transduction”Biochem J, 1995, 312(Pt 1):145-150.
Zohn, I.M. et al. “Rho family proteins and Ras transformation: the RHOad less traveled gets congested”Oncogene, 1998, 17:1415-1438.
McCormick, F.Nature, 1993, 363:15-16.
Campbell, S.L. et al.Oncogene, 1998, 17:1395-1413.
Barbacid, M.Annu. Rev. Biochem., 1987, 56:779-827.
Bos, J.L.Cancer Res., 1989, 49:4682-4689.
Olson, M.F. et al.A. Science, 1995, 269:1270-1272.
Qui, R.G. et al.Nature, 1995, 374:457-459.
Mellor, H. et al.J. Biol. Chem., 1998, 273:4811-4814.
Zhang, F.L. et al.Annu. Rev. Biochem., 1996, 65:241-269.
Lebowitz, P.F. et al.J. Biol. Chem., 1997, 272:15591-15594.
Sebti, S.M. et al.Pharmacol. Ther., 1997, 272:15591-15594.
Gibbs, J.B. et al.Annu. Rev. Pharmacol. Toxicol., 1997, 37:143-166.
Cox, A.D. et al.Biochim. Biophys. Acta., 1997, 1333:F51-F71.
Lebowitz, P.F. et al.Oncogene, 1998, 17:1439-1445.
Chen, Z. et al. “Famesylated and geranylgeranylated RhoB suppress the transformation of PANC-1 human pancreatic cancer cells” Proceedings of the 91stAnnual Meeting of the American Association of Cancer Research, vol. 14, p. 220, abstract No. 1402.
Liu and Jessell “A role for rhoB in the detamination of neural crest cells from the dorsal beural tubeȁ

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

RHoB as a suppressor of cancer cell growth, cell... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with RHoB as a suppressor of cancer cell growth, cell..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and RHoB as a suppressor of cancer cell growth, cell... will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-3667299

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.