Abstract
Cyclins and cyclin-dependent kinases may reflect the status of cell proliferation in cancer tissues. The authors sought to determine whether cdc2 and cyclin D1 are expressed in breast cancer and are useful as prognostic factors. Accumulation of cdc2 and cyclin D1 proteins was examined in 88 cases of breast cancer using immunoblotting techniques and correlations with clinicopathological factors and prognoses were investigated. Cdc2 and cyclin D1 proteins were observed in 27.3% and 75.0% of breast cancers studied, respectively. The incidence of lymph node metastasis was significantly high in cdc2/cyclin D1-double positive group and low in double negative group. On the other hand, the incidence of estrogen receptor (ER) negative cases was significantly higher in the cdc2-positive/cyclin D1-negative group. Relapse-free survival times of cdc2-positive cases were significantly shorter than those of cdc2-negative cases. The relapse-free survival times of cyclin D1-positive cases also tended to be poorer than those of cyclin D1-negative cases. Multivariate analyses revealed cdc2 as the second most significant of the prognostic variables, following lymph node status. The three-year relapse-free survival rate of cdc2/cyclin D1-double positive cases was 58.9%, whereas that of cdc2/cyclin D1-double negative cases was 100%. Cdc2 and cyclin D1 represent the status of cell proliferation in breast cancer, and may be useful in breast cancer assessment.
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Abbreviations
- ER:
-
Estrogen receptor
- PgR:
-
Progesterone receptor
References
Kallioniemi OP, Kallioniemi A, Kurisu W,et al: erbB2 amplification in breast cancer analyzed by fluorescence in situ hybridization.Proc Natl Acad Sci USA 89:5321–5325, 1992.
Borg A, Baldetorp B, Ferno M,et al: erbB2 amplification in breast cancer with a high rate of proliferation.Oncogene 6:137–143, 1991.
Coles C, Condie A, Chetty U,et al: p53 mutation in breast cancer.Cancer Res 52:5291–5298, 1992.
Runnebaum IB, Nagarajan M, Bowman M,et al: Mutation in p53 as potential molecular marker for human breast cancer.Proc Natl Acad Sci USA 88: 10657–10661, 1991.
Isola J, Visakorpi T, Holli K,et al: Association of overexpression of tumor suppressor protein p53 with rapid cell proliferation and poor prognosis in node-negative breast cancer patients.J Natl Cancer Inst 84:1109–1114, 1992.
Hartmann LC, Ingle JN, Wold LE,et al: Prognostic value of c-erbB2 overexpression in axillary lymph node positive breast cancer; Results from a randomized adjuvant treatment protocol.Cancer 74:2956–2963, 1994.
Lowenstein EJ, Daly RJ, Batzer AG,et al: The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling.Cell 70:431–442, 1992.
Li Y, Jenkins CW, Nichols MA,et al: Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21.Oncogene 9:2261–2268, 1994.
Hunter T, Pines J: Cyclins and cancer; Cyclin D and CDK inhibitors come of age.Cell 79:573–582, 1994.
Loyer P, Glaise D, Cariou S,et al: Expression and activation of cdks (1 and 2) and cyclins in the cell cycle progression during liver regeneration.J Biol Chem 269:2491–2500, 1994.
Stein GH, Drullinger LF, Robetorye RS,et al: Senescent cells fail to express cdc2, cycA, and cycB in response to mitogen stimulation.Proc Natl Acad Sci USA 88:11012–11016, 1991.
Ewen ME, Sluss HK, Sherr CJ,et al: Functional interactions of the retinoblastoma protein with mammalian D-type cyclins.Cell 73:487–497, 1993.
Hinds PW, Dowdy SF, Eaton EN,et al: Function of a human cyclin gene as an oncogene.Proc Natl Acad Sci USA 91:709–713, 1994.
Gillet C, Fantl V, Smith R,et al: Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining.Cancer Res 54:1812–1817, 1994.
Ohta T, Fukuda M, Arima K,et al: p34cdc2 as a breast cancer prognostic factor.J Jpn Soc Cancer Ther 31:107–115, 1996.
Ohta T, Fukuda M, Wanebo HJ,et al: Behavior of the cell cycle-associated proteins in an unusual G0-arrestable cancer cell line.Exp Cell Res 225:85–92, 1996.
Gasparini G, Boracchi P, Verderio P,et al: Cell kinetics in human breast cancer; Comparison between the prognostic value of the cytofluorimetric S-phase fraction and that of the antibodies to Ki-67 and PCNA antigens detected by immunocytochemistry.Int J Cancer 57:822–829, 1994.
Witzig TE, Ingle JN, Cha SS,et al: DNA ploidy and the percentage of cells in S-phase as prognostic factors for women with lymph node-negative breast cancer.Cancer 74:1752–1761, 1994.
van Dierendonck JH, Wijsman JH, Keijzer R,et al: Cell-cycle-related staining patterns of anti-proliferating cell nuclear monoclonal antibodies; Comparison with BRdU labeling and Ki-67 staining.Am J Pathol 138:1165–1172, 1991.
Draetta G, Beach D: Activation of cdc2 protein kinase during mitosis in human cells; Cell cycle dependent phosphorylation and subunit rearrangement.Cell 54:17–26, 1988.
Dunphy WG, Briznela L, Beach D,et al: The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis.Cell 54:423–431, 1988.
Draetta G, Luca F, Westendorf J,et al: cdc2 protein kinase is complexed with both cyclin A and B; Evidence for proteolytic inactivation of MPF.Cell 56:829–838, 1989.
Koff A, Giordano A, Desai D,et al: Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle.Science 257:1689–1694, 1992.
Devoto SH, Mudryj M, Pines J,et al: A cyclin A-protein kinase complex possesses sequence-specific DNA binding activity; p33cdk2 is a component of the E2F-cyclin A complex.Cell 68:167–176, 1992.
Buckley MF, Sweeney KJ, Hamilton JA,et al: Expression and amplification of cyclin genes in human breast cancer.Oncogene 8:2127–2133, 1993.
Sherr CJ: Mammalian G1 cyclins.Cell 73:1059–1065, 1993.
Tsuchiya A, Nihei M, Ando Y,et al: The relationship of estrogen receptor status to DNA ploidy in breast cancer.Surg Today 22:105–109, 1992.
Komaki K, Mori T, Morimoto T,et al: Correlation between estrogen receptor status and histological malignancy in human breast cancer.J Surg Oncol 46:185–189, 1991.
Hynes RO, Lander AD: Contact and adhesive specificities in the associations, migrations, and targeting of cells and axons.Cell 68:303–322, 1992.
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Ohta, T., Fukuda, M., Arima, K. et al. Analysis of Cdc2 and Cyclin D1 expression in breast cancer by immunoblotting. Breast Cancer 4, 17–24 (1997). https://doi.org/10.1007/BF02967050
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DOI: https://doi.org/10.1007/BF02967050