Abstract
P53 and cyclin D1 are interacting regulatory genes and both are frequently altered in breast cancer. We analysed p53 mutation by SSCP and sequencing methods as well as p53 protein accumulation immunohistochemically in 34 consecutively operated breast tumors. None of 4 fibroadenomas revealed p53 mutation or p53 protein accumulation. Mutation of p53 was present in 7 carcinomas. Immunohistochemistry revealed accumulation of p53 protein in 6 carcinomas and there was a significant correlation between p53 mutation and protein accumulation. Overexpression of cyclin D1 protein was observed in 11 carcinomas by immunohistochemistry and no correlation was observed between cyclin D1 overexpression and p53 mutation or accumulation. Our data support the concept that the p53-cyclin D1 signal pathway and the cyclin D1 cascade are disregulated in breast cancer.
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References
Andersen TI, Holm R, Nesland JM, et al: Prognostic significance of TP53 alterations in breast carcinoma. Br J Cancer 68:540–548, 1993.
Bates S, Parry D, Bonetta L, et al: Absence of cyclin D/cdk complexes in cells lacking functional retinoblastoma protein. Oncogene 9:1633–1640, 1994.
Bankfalvi A, Navabi H, Bier B, et al: Wet autoclave pretreatment for antigen retrieval in diagnostic immunohistochemistry. J Pathol 174:223–228, 1994.
Chen X, Bargonetti J, Prives C, et al: P53, through p21 (WAF1/CIP1) induces cyclin D1 synthesis. Cancer Res 55:4257–6342, 1995.
Cordon-Cardo C: Mutation of cell cycle regulators. Am J Pathol 147:545–560, 1995.
El-Deiry WS, Tokino T, Velculescu VE, et al: WAF1, a potential mediator of p53 tumor suppression. Cell75:817–825, 1993.
Fantl V, Smith R, Brokes S, et al: Chromosome 1 1q13 abnormalities in human breast cancer. Cancer Surv 18:77–94, 1993.
Gillett C, Smith P, Gregory W, et al: Cyclin D1 and prognosis in human breast cancer. Int J Cancer 69:92–99, 1996.
Ggrana K, Reddy EP: Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 11:211–219, 1995.
Greenblatt MS, Bennett WP, Hollstein M, et al: Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54:4855–4878, 1994.
Hollstein M, Sidransky D, Vogelstein B, et al: p53 mutation in human cancers. Science 253:49–53, 1991.
Jacquemier J, Moles JP, Adelaide J, et al: P53 immunohisto-chemical analysis in breast cancer with four monoclonal antibodies: comparison of staining and PCR-SSCP results. Br J Cancer 89:846–852, 1994.
Kastan MB, Zhan Q, El-Deiry WS, et al: A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-teleangiectasia. Cell 71:587–597, 1992.
Kovach JS, Hartmann A, Blaszik H, et al: Mutation detection by highly sensitive method indicates that p53 gene mutations in breast cancer can have important prognostic value. Proc Natl Acad Sci USA 93:1093–1096, 1996.
Kranenburg O, van der Eb AJ, Zantema A: Cyclin D1 is an essential mediator of apoptotic neuronal cell death. EMBO J 15:46–54, 1996.
Lane DP: P53 guardien of genome. Nature 359:15–16, 1992.
Li Y, Jenkins C, Nichols M, et al: Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. Oncogene 9:2261–2268, 1994.
Lidereau R, Mathieu D, Escot C, et al: Genetic variability of proto-oncogenes for breast cancer risk and prognosis. Biochemie 70:951–959, 1988.
Lucibello FC, Sewing A, Brusselbach S, et al: Deregulation of cyclin D1 and E and suppression of cdk2 and cdk4 in senescenct human fibroblasts. J Cell Sci 105:123–133, 1993.
Matsushime H, Quelle DE, Shurtleff SA, et al: D-type cyclin-dependent kinase activity in mammalian cells. Mol Cell Biol 14:2066–2076, 1994.
McIntosh GG, Anderson JJ, Milton I, et al: Determination of the prognostic value of cyclin D1 overexpression in breast cancer. Oncogene 11:885–891, 1995.
Michalides R, Hageman P, Tinteren H, et al: A clinicopathological study on overexpression of cyclin D1 and p53 in a series of 248 patients with operable breast cancer. Brit J Cancer 73:728–734, 1996.
Schauer IE, Siriwardana S, Langan TA, et al: Cyclin D1 over-expression vs. retinoblastoma inactivation: implications for growth control evasion in non-small cell and small cell lung cancer. Proc Natl Acad Sci USA 91:7827–7831, 1994.
Shuuring E, Verhoeven E, van Tinteren H, et al: Amplification of genes within the chromosome 11q13 region is indicative of poor prognosis in patients with operable breast cancer. Cancer Res 52:5229–5234, 1992.
Thor AD, Moore DH, Edgerton SM, et al: Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancer. JNCI 84:845–855, 1992.
Toguchida J, Yamaguchi T, Rithchie B, et al: Mutation spectrum of the p53 gene in bone and soft tissue sarcomas. Cancer Res 52:6194–6199, 1992.
Vogelstein B, Kinzler KW: P53 function and disfunction. Cell 70:523–526, 1992.
Waga S, Hannon GJ, Beach D, et al: The p21 inhibitor of cyclin dependent kinases controls DNA replication by interaction with PCNA. Nature 369:574–578, 1994.
Wang TC, Cardiff RD, Zukerberg L, et al: Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 369:669–671, 1994.
Wu X, Bayle JH, Olson D, et al: The p53-mdm2 autoregulatory feedback loop. Genes Dev 7:1126–1132, 1993.
Xiong Y, Hannon GJ, Zhang H, et al: P21 is a universal inhibitor of cyclin kinases. Nature 366:701–704, 1993.
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Tanyi, J., Tory, K., BÁnkfalvi, A. et al. Analysis of p53 mutation and cyclin d1 expression in breast tumors. Pathol. Oncol. Res. 5, 90–94 (1999). https://doi.org/10.1053/paor.1999.0201
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DOI: https://doi.org/10.1053/paor.1999.0201