RESUMO
Expression of cyclins A, B1 and D1 in human breast cancer was analyzed using dual-parameter flow cytometry with simultaneous evaluation of the DNA content. The asynchronous MCF-7 breast adenocarcinoma cells were used to implement flow cytometry analysis and to analyze the cell cycle distribution of cyclins. The patterns of the cyclin expression were also analyzed in vivo in fresh tissue specimens of human breast carcinomas. The combined measurement of DNA and cyclins showed a higher cyclin expression in aneuploid (11.5 +/- 2.0%, 4.3 +/- 1.1%, and 19.5 +/- 3.4% positive cells for cyclins A, B, and D1, respectively) than in diploid carcinomas (3.9 +/- 1.2%, 1.1 +/- 0.4%, and 5.0 +/- 1.2% positive cells for cyclins A, B, and D1, respectively). A positive relationship was also found between cyclin A and D1 expression and H(3)-thymidine labeling index. In the in vitro model, the asynchronous growing MCF-7 cells showed a variable number of cells expressing cyclins in an unscheduled way, unrelated to the phase at which these cyclins are expressed in normal cells. A similar condition was also observed in tumors. In conclusion, the data showed a deregulated expression of cyclins in a transformed adenocarcinoma cell line and in breast tumors. Furthermore, overexpression of these proteins is related to the aneuploid and high proliferative activity of human mammary carcinomas.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular , Ciclinas/metabolismo , Aneuploidia , Neoplasias da Mama/genética , Divisão Celular , Ciclina A/metabolismo , Ciclina B/metabolismo , Ciclina B1 , Ciclina D1/metabolismo , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Feminino , Citometria de Fluxo , Fase G1 , Fase G2 , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mitose , Fase S , Células Tumorais CultivadasRESUMO
Cyclin-D1 (CD1) expression was analyzed in human mammary carcinomas by immunohistochemical (IHC) and flow-cytometry (FCM) methods: 52.5% and 50% of cases were strong expressors of CD1 by IHC and FCM analysis respectively. The percentage of CD1-positive cells was especially high in node-negative (N-) estrogen-receptor-positive (ER+) tumors, probably as a consequence of CD1 induction by estrogens in steroid-responsive tissues. However, CD1 expression was not related to ER positivity in node-positive tumors (N+). An interesting relationship between CD1 expression and H3-thymidine labelling index (H3Td-LI) was also found: CD1 and H3Td-LI were unrelated in N- tumors, while high CD1 expression was observed in N+ tumors with high DNA synthesis, as assessed by H3Td-LI. The combined measurement of DNA and CD1 showed that 27 specimens were aneuploid, 19 of them (19/27; 70%) strongly expressing CD1. Further studies are needed to clarify the role of CD1 in DNA abnormality of breast tumors. However, we cannot exclude that the CD1 may be differently de-regulated in the last phase of tumor progression, and that CD1 over-expression may contribute to the aneuploidy of mammary carcinomas.