Tumor escape in a Wnt1-dependent mouse breast cancer model is enabled by p19Arf/p53 pathway lesions but not p16Ink4a loss

Journal of Clinical Investigation

Volumn 118, Issue 1, 2008, Pages 51-63

  Debies, Michael T ^a   Gestl, Shelley A ^a   Mathers, Jessica L ^a   Mikse, Oliver R ^a   Leonard, Travis L ^a   Moody, Susan E ^b   Chodosh, Lewis A ^b   Cardiff, Robert D ^c   Gunther, Edward J ^a,d  

^a PENN STATE CANCER INSTITUTE   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d PENN STATE COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA CATENIN; CYCLIN D1; CYCLIN DEPENDENT KINASE INHIBITOR 2A; PROTEIN P19; PROTEIN P53; WNT1 PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BREAST CANCER; CANCER RELAPSE; CARCINOGENESIS; CONTROLLED STUDY; GENE EXPRESSION; GENE MUTATION; GENOMIC INSTABILITY; GERM LINE; MOUSE; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; PROTEIN DEFICIENCY; TUMOR SUPPRESSOR GENE;

ALLELES; ANIMALS; CYCLIN-DEPENDENT KINASE INHIBITOR P16; FEMALE; GENOMIC INSTABILITY; MAMMARY NEOPLASMS, EXPERIMENTAL; MICE; MICE, TRANSGENIC; MUTATION; RECURRENCE; SIGNAL TRANSDUCTION; TUMOR ESCAPE; TUMOR SUPPRESSOR PROTEIN P53; WNT1 PROTEIN;

EID: 38349078213     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI33320     Document Type: Article

References (57)

1. Cordera, F., and Jordan, V.C. 2006. Steroid receptors and their role in the biology and control of breast cancer growth. Semin. Oncol. 33:631-641.
2. Slamon, D.J., Romond, E.H., and Perez, E.A. 2006. Advances in adjuvant therapy for breast cancer. Clin. Adv. Hematol. Oncol. 4(Suppl. 1):4-9; discussion, Suppl. 10; quiz following Suppl. 10.
3. Hingorani, S.R., and Tuveson, D.A. 2003. Targeting oncogene dependence and resistance. Cancer Cell. 3:414-417.
4. Nicholson, R.I., and Johnston, S.R. 2005. Endocrine therapy - current benefits and limitations. Breast Cancer Res. Treat. 93(Suppl. 1):S3-S10.
5. Nahta, R., and Esteva, F.J. 2006. HER2 therapy: molecular mechanisms of trastuzumab resistance. Breast Cancer Res. 8:215.
6. Dodwell, D., and Vergote, I. 2005. A comparison of fulvestrant and the third-generation aromatase inhibitors in the second-line treatment of postmenopausal women with advanced breast cancer. Cancer Treat. Rev. 31:274-282.
7. Geyer, C.E., et al. 2006. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N. Engl. J. Med. 355:2733-2743.
8. Gee, J.M., et al. 2005. Consensus statement. Workshop on therapeutic resistance in breast cancer: impact of growth factor signalling pathways and implications for future treatment. Endocr. Relat. Cancer. 12(Suppl. 1):S1-S7.
9. Nagata, Y., et al. 2004. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 6:117-127.
10. Sergina, N.V., et al. 2007. Escape from HER-family tyrosine kinase inhibitor therapy by the kinasein-active HER3. Nature. 445:437-441.
11. Moy, B., and Goss, P.E. 2006. Lapatinib: current status and future directions in breast cancer. Oncologist. 11:1047-1057.
12. Sharpless, N.E., and Depinho, R.A. 2006. The mighty mouse: genetically engineered mouse models in cancer drug development. Nat. Rev. Drug Discov. 5:741-754.
13. Schmitt, C.A., et al. 2002. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell. 109:335-346.
14. Schmitt, C.A., et al. 2002. Dissecting p53 tumor suppressor functions in vivo. Cancer Cell. 1:289-298.
15. Gunther, E.J., et al. 2003. Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis. Genes Dev. 17:488-501.
16. Giuriato, S., et al. 2006. Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch. Proc. Natl. Acad. Sci. U. S. A. 103:16266-16271.
17. Crawford, Y.G., et al. 2004. Histologically normal human mammary epithelia with silenced p16(INK4a) overexpress COX-2, promoting a premalignant program. Cancer Cell. 5:263-273.
18. Polakis, P. 2000. Wnt signaling and cancer. Genes Dev. 14:1837-1851.
19. Jho, E.H., et al. 2002. Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol. Cell. Biol. 22:1172-1183.
20. Lustig, B., et al. 2002. Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Mol. Cell. Biol. 22:1184-1193.
21. Honoré, S.M., Aybar, M.J., and Mayor, R. 2003. Sox10 is required for the early development of the prospective neural crest in Xenopus embryos. Dev. Biol. 260:79-96.
22. Yan, D., et al. 2001. Elevated expression of axin2 and hnkd mRNA provides evidence that Wnt/beta-catenin signaling is activated in human colon tumors. Proc. Natl. Acad. Sci. U. S. A. 98:14973-14978.
23. de La Coste, A., et al. 1998. Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc. Natl. Acad. Sci. U. S. A. 95:8847-8851.
24. Batlle, E., et al. 2000. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat. Cell Biol. 2:84-89.
25. Cano, A., et al. 2000. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat. Cell Biol. 2:76-83.
26. Sadot, E., Geiger, B., Oren, M., and Ben-Ze'ev, A. 2001. Down-regulation of beta-catenin by activated p53. Mol. Cell. Biol. 21:6768-6781.
27. Jacks, T., et al. 1994. Tumor spectrum analysis in p53-mutant mice. Curr. Biol. 4:1-7.
28. Lowe, S.W., and Sherr, C.J. 2003. Tumor suppression by Ink4a-Arf: progress and puzzles. Curr. Opin. Genet. Dev. 13:77-83.
29. Dominguez, G., et al. 2003. Prevalence of aberrant methylation of p14ARF over p16INK4a in some human primary tumors. Mutat. Res. 530:9-17.
30. Silva, J., et al. 2003. Concomitant expression of p16INK4a and p14ARF in primary breast cancer and analysis of inactivation mechanisms. J. Pathol. 199:289-297.
31. Serrano, M., et al. 1996. Role of the INK4a locus in tumor suppression and cell mortality. Cell. 85:27-37.
32. Rosner, A., et al. 2002. Pathway pathology: histological differences between ErbB/Ras and Wnt pathway transgenic mammary tumors. Am. J. Pathol. 161:1087-1097.
33. Bertwistle, D., and Sherr, C.J. 2007. Regulation of the Arf tumor suppressor in Emicro-Myc transgenic mice: longitudinal study of Myc-induced lymphomagenesis. Blood. 109:792-794.
34. Kamijo, T., et al. 1997. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell. 91:649-659.
35. Robertson, S.A., et al. 2005. Spectral karyotyping of sarcomas and fibroblasts derived from Ink4a/Arfdeficient mice reveals chromosomal instability in vitro. Int. J. Oncol. 26:629-634.
36. Sharpless, N.E., et al. 2001. Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis. Nature. 413:86-91.
37. Chin, L., and DePinho, R.A. 2000. Flipping the oncogene switch: illumination of tumor maintenance and regression. Trends Genet. 16:147-150.
38. Barker, N., and Clevers, H. 2006. Mining the Wnt pathway for cancer therapeutics. Nat. Rev. Drug Discov. 5:997-1014.
39. Bafico, A., Liu, G., Goldin, L., Harris, V., and Aaronson, S.A. 2004. An autocrine mechanism for constitutive Wnt pathway activation in human cancer cells. Cancer Cell. 6:497-506.
40. Schmitt, C.A., McCurrach, M.E., de Stanchina, E., Wallace-Brodeur, R.R., and Lowe, S.W. 1999. INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53. Genes Dev. 13:2670-2677.
41. Eischen, C.M., Weber, J.D., Roussel, M.F., Sherr, C.J., and Cleveland, J.L. 1999. Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev. 13:2658-2669.
42. Sharpless, N.E., Kannan, K., Xu, J., Bosenberg, M.W., and Chin, L. 2003. Both products of the mouse Ink4a/Arf locus suppress melanoma formation in vivo. Oncogene. 22:5055-5059.
43. Bardeesy, N., et al. 2006. Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc. Natl. Acad. Sci. U. S. A. 103:5947-5952.
44. D'Amico, M., et al. 2003. The role of Ink4a/Arf in ErbB2 mammary gland tumorigenesis. Cancer Res. 63:3395-3402.
45. Tolbert, D., Lu, X., Yin, C., Tantama, M., and Van Dyke, T. 2002. p19(ARF) is dispensable for oncogenic stress-induced p53-mediated apoptosis and tumor suppression in vivo. Mol. Cell. Biol. 22:370-377.
46. Vogelstein, B., Lane, D., and Levine, A.J. 2000. Surfing the p53 network. Nature. 408:307-310.
47. Wu, C.H., et al. 2007. Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation. Proc. Natl. Acad. Sci. U. S. A. 104:13028-13033.
48. Lu, X., et al. 2001. Selective inactivation of p53 facilitates mouse epithelial tumor progression without chromosomal instability. Mol. Cell. Biol. 21:6017-6030.
49. Williams, R.T., Roussel, M.F., and Sherr, C.J. 2006. Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Ablinduced acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. U. S. A. 103:6688-6693.
50. Wendel, H.G., et al. 2006. Loss of p53 impedes the antileukemic response to BCR-ABL inhibition. Proc. Natl. Acad. Sci. U. S. A. 103:7444-7449.
51. Linardopoulos, S., et al. 1995. Deletion and altered regulation of p16INK4a and p15INK4b in undifferentiated mouse skin tumors. Cancer Res. 55:5168-5172.
52. Nelson, W.J., and Nusse, R. 2004. Convergence of Wnt, beta-catenin, and cadherin pathways. Science. 303:1483-1487.
53. Vega, S., et al. 2004. Snail blocks the cell cycle and confers resistance to cell death. Genes Dev. 18:1131-1143.
54. Moody, S.E., et al. 2005. The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell. 8:197-209.
55. Miller, L.D., et al. 2005. An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. Proc. Natl. Acad. Sci. U. S. A. 102:13550-13555.
56. Vassilev, L.T., et al. 2004. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 303:844-848.
57. Marquis, S.T., et al. 1995. The developmental pattern of Brca1 expression implies a role in differentiation of the breast and other tissues. Nat. Genet. 11:17-26.