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Abstract:

TGF-β1 modulation of cell cycle components was assessed in an experimental model in which the synthetic progestin medroxyprogesterone acetate (MPA) induced mammary tumors in Balb/c mice. TGF-β1 inhibited both MPA-induced proliferation of progestin-dependent C4HD epithelial cells and proliferation of the progestin-independent variant cell type C4HI, arresting cells in G1 phase of the cell cycle. Progestin-independent 60 epithelial cells evidenced reduced response to TGF-β1 antiproliferative effects. TGF-β1 inhibition of cyclins D1 and A expression and up-regulation of p21CIP1 levels were the common findings in all three cell types. In addition, a significant content reduction of cyclin D1/cdk4 and cyclin A/cdk2 complexes was found after TGF-β1 inhibition of MPA-dependent and -independent proliferation. TGF-β1 inhibited cyclin D2 expression and up-regulated p27KIP1 levels only when acting as inhibitor of MPA-induced proliferation of C4HD cells. Regulation of these two cell cycle components resulted in decreased cyclin D2/ cdk2 complex and in increased p27KIP1 association with cdk2 in C4HD cells treated with TGF-β1. These two molecular mechanisms, unobserved in progestin-independent growth of C4HI or 60 cells, were associated with a significantly higher degree of inhibition of cdk2 kinase activity in C4HD cells compared to that found in TGF-β-treated C4HI or 60 cells. Reduced sensitivity of 60 cells to the growth-inhibitory effects of TGF-β1 correlated with significantly lower levels of p15INK4B p21CIP1, and p27KIP1 expressed in these cells, compared to the levels present in C4HD or C4HI cells, and correlated as well with lack of expression of p16INK4. Thus, common targets were found to exist in TGF-β1 inhibitory action on breast cancer cells, but regulation of specific targets was found when TGF-β1-inhibited proliferation driven by the progesterone receptor. © 2001 Academic Press.

Registro:

Documento: Artículo
Título:Mechanisms of cell cycle arrest in response to TGF-β in progestin- dependent and -independent growth of mammary tumors
Autor:Salatino, M.; Labriola, L.; Schillaci, R.; Charreau, E.H.; Elizalde, P.V.
Filiación:Instituto de Biología y Medicina Experimental, Obligado 2490, Buenos Aires, 1428, Argentina
Facultad de Ciencias Exactus y Naturales, Universidad de Buenos Aires, Argentina
Palabras clave:Cell cycle; Mammary tumors; Progestins; Transforming growth factor-β(TGF-β); cyclin A; cyclin D1; medroxyprogesterone acetate; progesterone receptor; protein p21; transforming growth factor beta1; animal cell; animal experiment; animal model; article; breast tumor; cell cycle; cell cycle G1 phase; cell proliferation; cell type; controlled study; experimental model; female; molecular dynamics; mouse; nonhuman; priority journal; protein expression
Año:2001
Volumen:265
Número:1
Página de inicio:152
Página de fin:166
DOI: http://dx.doi.org/10.1006/excr.2001.5175
Título revista:Experimental Cell Research
Título revista abreviado:Exp. Cell Res.
ISSN:00144827
CODEN:ECREA
CAS:medroxyprogesterone acetate, 71-58-9; protein p21, 85306-28-1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00144827_v265_n1_p152_Salatino

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Citas:

---------- APA ----------
Salatino, M., Labriola, L., Schillaci, R., Charreau, E.H. & Elizalde, P.V. (2001) . Mechanisms of cell cycle arrest in response to TGF-β in progestin- dependent and -independent growth of mammary tumors. Experimental Cell Research, 265(1), 152-166.
http://dx.doi.org/10.1006/excr.2001.5175
---------- CHICAGO ----------
Salatino, M., Labriola, L., Schillaci, R., Charreau, E.H., Elizalde, P.V. "Mechanisms of cell cycle arrest in response to TGF-β in progestin- dependent and -independent growth of mammary tumors" . Experimental Cell Research 265, no. 1 (2001) : 152-166.
http://dx.doi.org/10.1006/excr.2001.5175
---------- MLA ----------
Salatino, M., Labriola, L., Schillaci, R., Charreau, E.H., Elizalde, P.V. "Mechanisms of cell cycle arrest in response to TGF-β in progestin- dependent and -independent growth of mammary tumors" . Experimental Cell Research, vol. 265, no. 1, 2001, pp. 152-166.
http://dx.doi.org/10.1006/excr.2001.5175
---------- VANCOUVER ----------
Salatino, M., Labriola, L., Schillaci, R., Charreau, E.H., Elizalde, P.V. Mechanisms of cell cycle arrest in response to TGF-β in progestin- dependent and -independent growth of mammary tumors. Exp. Cell Res. 2001;265(1):152-166.
http://dx.doi.org/10.1006/excr.2001.5175