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Can transforming growth factor-beta1 and retinoids modify the activity of estradiol and antiestrogens in MCF-7 breast cancer cells?.

Abstract

Retinoic acid and transforming growth factor-beta (TGF-beta) affect differentiation, proliferation and carcinogenesis of epithelial cells. The effect of both compounds on the proliferation of cells of the hormone sensitive human breast cancer cell line (ER+) MCF-7 was assessed in the presence of estradiol and tamoxifen. The assay was based on [3H]thymidine incorporation and the proliferative activity of PCNA- and Ki 67-positive cells. The apoptotic index and expression of the Bcl-2 and p53 antigens in MCF-7 cells were also determined. Exogenous TGF-beta1 added to the cell culture showed antiproliferative activity within the concentration range of 0.003-30 ng/ml. Irrespective of TGF-beta1 concentrations, a marked reduction in the stimulatory action of estradiol (10(-9) and 10(-8) M) was observed whereas in combination with tamoxifen (10(-7) and 10(-6) M) only 30 ng/ml TGF-beta1 caused a statistically significant reduction to approximately 30% of the proliferative cells. In further experiments we examined the effect of exposure of breast cancer cells to retinoids in combination with TGF-beta1. The incorporation of [3H]thymidine into MCF-7 cells was inhibited to 52 +/- 19% (control =100%) by 3 ng/ml TGF-beta1, and this dose was used throughout. It was found that addition of TGF-beta1 and isotretinoin to the culture did not decrease proliferation, while TGF-beta1 and tretinoin at low concentrations (3 x 10(-8) and 3 x 10(-7) M) reduced the percentage of proliferating cells by approximately 30% (67+/-8% and 67+/-5%, P<0.05 compared to values in the tretinoin group). Both retinoids also led to a statistically significant decrease in the stimulatory effect of 10(-9) M estradiol, attenuated by TGF-beta1. In addition, the retinoids in combination with TGF-beta1 and tamoxifen (10(-6) M) caused a further reduction in the percentage of proliferating cells. Immunocytochemical analysis showed that all the examined compounds gave a statistically significant reduction in the percentage of cells with a positive reaction to PCNA and Ki 67 antigen. TGF-beta1, isotretinoin and tretinoin added to the culture resulted in the lowest percentage of PCNA positive cells. However, the lowest fraction of Ki 67 positive cells was observed after addition of isotretinoin. The obtained results also confirm the fact that the well-known regulatory proteins Bcl-2 and p53 play an important role in the regulation of apoptosis in the MCF-7 cell line, with lowered Bcl-2 expression accompanying easier apoptotic induction. The majority of the examined compounds act via the p53 pathway although some bypass this important proapoptotic factor.

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    ,

    Department of Gynaecological Endocrinology, Medical University of Białystok, Białystok, Poland. czeczuga@wp.pl

    , , ,

    Source

    Acta biochimica Polonica 51:3 2004 pg 733-45

    MeSH

    Apoptosis
    Breast Neoplasms
    Cell Line, Tumor
    Cell Proliferation
    Estradiol
    Estrogen Receptor Modulators
    Female
    Humans
    Isotretinoin
    Ki-67 Antigen
    Proliferating Cell Nuclear Antigen
    Proto-Oncogene Proteins c-bcl-2
    Tamoxifen
    Thymidine
    Transforming Growth Factor beta
    Transforming Growth Factor beta1
    Tretinoin
    Tumor Suppressor Protein p53

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    15448735

    Citation

    Czeczuga-Semeniuk, Ewa, et al. "Can Transforming Growth Factor-beta1 and Retinoids Modify the Activity of Estradiol and Antiestrogens in MCF-7 Breast Cancer Cells?." Acta Biochimica Polonica, vol. 51, no. 3, 2004, pp. 733-45.
    Czeczuga-Semeniuk E, Anchim T, Dziecioł J, et al. Can transforming growth factor-beta1 and retinoids modify the activity of estradiol and antiestrogens in MCF-7 breast cancer cells?. Acta Biochim Pol. 2004;51(3):733-45.
    Czeczuga-Semeniuk, E., Anchim, T., Dziecioł, J., Dabrowska, M., & Wołczyński, S. (2004). Can transforming growth factor-beta1 and retinoids modify the activity of estradiol and antiestrogens in MCF-7 breast cancer cells?. Acta Biochimica Polonica, 51(3), pp. 733-45.
    Czeczuga-Semeniuk E, et al. Can Transforming Growth Factor-beta1 and Retinoids Modify the Activity of Estradiol and Antiestrogens in MCF-7 Breast Cancer Cells?. Acta Biochim Pol. 2004;51(3):733-45. PubMed PMID: 15448735.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Can transforming growth factor-beta1 and retinoids modify the activity of estradiol and antiestrogens in MCF-7 breast cancer cells?. AU - Czeczuga-Semeniuk,Ewa, AU - Anchim,Tomasz, AU - Dziecioł,Janusz, AU - Dabrowska,Milena, AU - Wołczyński,Sławomir, PY - 2003/01/02/received PY - 2003/12/03/revised PY - 2004/02/26/accepted PY - 2004/9/28/pubmed PY - 2005/3/30/medline PY - 2004/9/28/entrez SP - 733 EP - 45 JF - Acta biochimica Polonica JO - Acta Biochim. Pol. VL - 51 IS - 3 N2 - Retinoic acid and transforming growth factor-beta (TGF-beta) affect differentiation, proliferation and carcinogenesis of epithelial cells. The effect of both compounds on the proliferation of cells of the hormone sensitive human breast cancer cell line (ER+) MCF-7 was assessed in the presence of estradiol and tamoxifen. The assay was based on [3H]thymidine incorporation and the proliferative activity of PCNA- and Ki 67-positive cells. The apoptotic index and expression of the Bcl-2 and p53 antigens in MCF-7 cells were also determined. Exogenous TGF-beta1 added to the cell culture showed antiproliferative activity within the concentration range of 0.003-30 ng/ml. Irrespective of TGF-beta1 concentrations, a marked reduction in the stimulatory action of estradiol (10(-9) and 10(-8) M) was observed whereas in combination with tamoxifen (10(-7) and 10(-6) M) only 30 ng/ml TGF-beta1 caused a statistically significant reduction to approximately 30% of the proliferative cells. In further experiments we examined the effect of exposure of breast cancer cells to retinoids in combination with TGF-beta1. The incorporation of [3H]thymidine into MCF-7 cells was inhibited to 52 +/- 19% (control =100%) by 3 ng/ml TGF-beta1, and this dose was used throughout. It was found that addition of TGF-beta1 and isotretinoin to the culture did not decrease proliferation, while TGF-beta1 and tretinoin at low concentrations (3 x 10(-8) and 3 x 10(-7) M) reduced the percentage of proliferating cells by approximately 30% (67+/-8% and 67+/-5%, P<0.05 compared to values in the tretinoin group). Both retinoids also led to a statistically significant decrease in the stimulatory effect of 10(-9) M estradiol, attenuated by TGF-beta1. In addition, the retinoids in combination with TGF-beta1 and tamoxifen (10(-6) M) caused a further reduction in the percentage of proliferating cells. Immunocytochemical analysis showed that all the examined compounds gave a statistically significant reduction in the percentage of cells with a positive reaction to PCNA and Ki 67 antigen. TGF-beta1, isotretinoin and tretinoin added to the culture resulted in the lowest percentage of PCNA positive cells. However, the lowest fraction of Ki 67 positive cells was observed after addition of isotretinoin. The obtained results also confirm the fact that the well-known regulatory proteins Bcl-2 and p53 play an important role in the regulation of apoptosis in the MCF-7 cell line, with lowered Bcl-2 expression accompanying easier apoptotic induction. The majority of the examined compounds act via the p53 pathway although some bypass this important proapoptotic factor. SN - 0001-527X UR - https://www.unboundmedicine.com/medline/citation/15448735/Can_transforming_growth_factor_beta1_and_retinoids_modify_the_activity_of_estradiol_and_antiestrogens_in_MCF_7_breast_cancer_cells_ L2 - http://www.actabp.pl/pdf/3_2004/733.pdf DB - PRIME DP - Unbound Medicine ER -