scholarly journals Possible involvement of bcl-2 in regulation of cell-cycle progression of haemopoietic cells by transforming growth factor-beta1

1999 ◽  
Vol 105 (2) ◽  
pp. 470-477 ◽  
Author(s):  
Nadim Mahmud ◽  
Naoyuki Katayama ◽  
Kazuhiro Nishii ◽  
Takayuki Sugawara ◽  
Yoshihiro Komada ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Progression ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Beta1 ◽  
Cycle Progression ◽  
Regulation Of Cell Cycle ◽  
Haemopoietic Cells

scholarly journals The Activity of Differentiation Factors Induces Apoptosis in Polyomavirus Large T-Expressing Myoblasts

1998 ◽  
Vol 9 (6) ◽  
pp. 1449-1463 ◽  
Author(s):  
Gian Maria Fimia ◽  
Vanesa Gottifredi ◽  
Barbara Bellei ◽  
Maria Rosaria Ricciardi ◽  
Agostino Tafuri ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Growth Factor ◽  
Cell Cycle Progression ◽  
Transforming Growth Factor ◽  
Myogenic Differentiation ◽  
Transforming Growth Factor Β ◽  
Large Tumor ◽  
Cycle Progression

It is commonly accepted that pathways that regulate proliferation/differentiation processes, if altered in their normal interplay, can lead to the induction of programmed cell death. In a previous work we reported that Polyoma virus Large Tumor antigen (PyLT) interferes with in vitro terminal differentiation of skeletal myoblasts by binding and inactivating the retinoblastoma antioncogene product. This inhibition occurs after the activation of some early steps of the myogenic program. In the present work we report that myoblasts expressing wild-type PyLT, when subjected to differentiation stimuli, undergo cell death and that this cell death can be defined as apoptosis. Apoptosis in PyLT-expressing myoblasts starts after growth factors removal, is promoted by cell confluence, and is temporally correlated with the expression of early markers of myogenic differentiation. The block of the initial events of myogenesis by transforming growth factor β or basic fibroblast growth factor prevents PyLT-induced apoptosis, while the acceleration of this process by the overexpression of the muscle-regulatory factor MyoD further increases cell death in this system. MyoD can induce PyLT-expressing myoblasts to accumulate RB, p21, and muscle- specific genes but is unable to induce G00arrest. Several markers of different phases of the cell cycle, such as cyclin A, cdk-2, and cdc-2, fail to be down-regulated, indicating the occurrence of cell cycle progression. It has been frequently suggested that apoptosis can result from an unbalanced cell cycle progression in the presence of a contrasting signal, such as growth factor deprivation. Our data involve differentiation pathways, as a further contrasting signal, in the generation of this conflict during myoblast cell apoptosis.

Bcr-Abl kinase down-regulates cyclin-dependent kinase inhibitor p27 in human and murine cell lines

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1933-1939 ◽  
Author(s):  
Tarja Jonuleit ◽  
Heiko van der Kuip ◽  
Cornelius Miething ◽  
Heike Michels ◽  
Michael Hallek ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
Down Regulation ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases ◽  
Abl Kinase

Abstract Chronic myeloid leukemia (CML) is a malignant stem cell disease characterized by an expansion of myeloid progenitor cells expressing the constitutively activated Bcr-Abl kinase. This oncogenic event causes a deregulation of apoptosis and cell cycle progression. Although the molecular mechanisms protecting from apoptosis in CML cells are well characterized, the cell cycle regulatory event is poorly understood. An inhibitor of the cyclin-dependent kinases, p27, plays a central role in the regulation of growth factor dependent proliferation of hematopoietic cells. Therefore, we have analyzed the influence of Bcr-Abl in the regulation of p27 expression in various hematopoietic cell systems. An active Bcr-Abl kinase causes down-regulation of p27 expression in murine Ba/F3 cells and human M07 cells. Bcr-Abl blocks up-regulation of p27 after growth factor withdrawal and serum reduction. In addition, p27 induction by transforming growth factor-beta (TGF-β) is completely blocked in Bcr-Abl positive M07/p210 cells. This deregulation is directly mediated by the activity of the Bcr-Abl kinase. A Bcr-Abl kinase inhibitor completely abolishes p27 down-regulation by Bcr-Abl in both Ba/F3 cells transfected either with a constitutively active Bcr-Abl or with a temperature sensitive mutant. The down-regulation of p27 by Bcr-Abl depends on proteasomal degradation and can be blocked by lactacystin. Overexpression of wild-type p27 partially antagonizes Bcr-Abl–induced proliferation in Ba/F3 cells. We conclude that Bcr-Abl promotes cell cycle progression and activation of cyclin-dependent kinases by interfering with the regulation of the cell cycle inhibitory protein p27.

scholarly journals Progestins both stimulate and inhibit breast cancer cell cycle progression while increasing expression of transforming growth factor alpha, epidermal growth factor receptor, c-fos, and c-myc genes

1991 ◽  
Vol 11 (10) ◽  
pp. 5032-5043
Author(s):  
E A Musgrove ◽  
C S Lee ◽  
R L Sutherland
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Cycle Progression ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Alpha ◽  
Cycle Progression ◽  
Epidermal Growth ◽  
Factor Alpha

This study documents a biphasic change in the rate of cell cycle progression and proliferation of T-47D human breast cancer cells treated with synthetic progestins, consisting of an initial transient acceleration in transit through G1, followed by cell cycle arrest and growth inhibition. Both components of the response were mediated via the progesterone receptor. The data are consistent with a model in which the action of progestins is to accelerate cells already progressing through G1, which are then arrested early in G1 after completing a round of replication, as are cells initially in other phases of the cell cycle. Such acceleration implies that progestins act on genes or gene products which are rate limiting for cell cycle progression. Increased production of epidermal growth factor and transforming growth factor alpha, putative autocrine growth factors in breast cancer cells, does not appear to account for the initial response to progestins, since although the mRNA abundance for these growth factors is rapidly induced by progestins, cells treated with epidermal growth factor or transforming growth factor alpha did not enter S phase until 5 to 6 h later than those stimulated by progestin. The proto-oncogenes c-fos and c-myc were rapidly but transiently induced by progestin treatment, paralleling the well-known response of these genes to mitogenic signals in other cell types. The progestin antagonist RU 486 inhibited progestin regulation of both cell cycle progression and c-myc expression, suggesting that this proto-oncogene may participate in growth modulation by progestins.

Bcr-Abl kinase down-regulates cyclin-dependent kinase inhibitor p27 in human and murine cell lines

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1933-1939 ◽  
Author(s):  
Tarja Jonuleit ◽  
Heiko van der Kuip ◽  
Cornelius Miething ◽  
Heike Michels ◽  
Michael Hallek ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
Down Regulation ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases ◽  
Abl Kinase

Chronic myeloid leukemia (CML) is a malignant stem cell disease characterized by an expansion of myeloid progenitor cells expressing the constitutively activated Bcr-Abl kinase. This oncogenic event causes a deregulation of apoptosis and cell cycle progression. Although the molecular mechanisms protecting from apoptosis in CML cells are well characterized, the cell cycle regulatory event is poorly understood. An inhibitor of the cyclin-dependent kinases, p27, plays a central role in the regulation of growth factor dependent proliferation of hematopoietic cells. Therefore, we have analyzed the influence of Bcr-Abl in the regulation of p27 expression in various hematopoietic cell systems. An active Bcr-Abl kinase causes down-regulation of p27 expression in murine Ba/F3 cells and human M07 cells. Bcr-Abl blocks up-regulation of p27 after growth factor withdrawal and serum reduction. In addition, p27 induction by transforming growth factor-beta (TGF-β) is completely blocked in Bcr-Abl positive M07/p210 cells. This deregulation is directly mediated by the activity of the Bcr-Abl kinase. A Bcr-Abl kinase inhibitor completely abolishes p27 down-regulation by Bcr-Abl in both Ba/F3 cells transfected either with a constitutively active Bcr-Abl or with a temperature sensitive mutant. The down-regulation of p27 by Bcr-Abl depends on proteasomal degradation and can be blocked by lactacystin. Overexpression of wild-type p27 partially antagonizes Bcr-Abl–induced proliferation in Ba/F3 cells. We conclude that Bcr-Abl promotes cell cycle progression and activation of cyclin-dependent kinases by interfering with the regulation of the cell cycle inhibitory protein p27.

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