scholarly journals PTEN insufficiency modulates ER+ breast cancer cell cycle progression and increases cell growth in vitro and in vivo

2015 ◽  
pp. 4631 ◽  
Author(s):  
Kun-Chun Chiang ◽  
Chun-Nan Yeh ◽  
Huang-Yang Chen ◽  
Jong-Hwei S.Pang ◽  
Shang-Yu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Cycle Progression ◽  
Cycle Progression

scholarly journals Roquin1 Suppresses Breast Cancer Growth by Inducing Cell Cycle Arrest via Selectively Destabilizing Cell Cycle–Promoting Gene mRNAs

2020 ◽  
Author(s):  
Wenbao Lu ◽  
Meicen Zhou ◽  
Bing Wang ◽  
Xueting Liu ◽  
Bingwei Li
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Breast Cancer Cell ◽  
Breast Tumor ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Cycle Arrest

Abstract Background: Dysregulation of cell cycle progression is one of the common features of human cancer cells, however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest induction in breast cancer.Methods: Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and the significant association with patient survival. Quantitative real-time PCR and western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assay, flow cytometry, and in vivo study were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA-sequencing was applied to identify the differential genes and pathways regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1.Results: We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse free survival of patients with breast cancer. Roquin1 overexpression inhibited breast cancer cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted breast cancer cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizing cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2) through targeting the stem–loop structure in the 3’untranslated region (3’UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs.Conclusions: Our findings demonstrated that Roquin1 was a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might as a potential molecular target for breast cancer treatment.

scholarly journals Growth factor, steroid, and steroid antagonist regulation of cyclin gene expression associated with changes in T-47D human breast cancer cell cycle progression.

1993 ◽  
Vol 13 (6) ◽  
pp. 3577-3587 ◽  
Author(s):  
E A Musgrove ◽  
J A Hamilton ◽  
C S Lee ◽  
K J Sweeney ◽  
C K Watts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Cycle Progression ◽  
S Phase ◽  
G1 Phase ◽  
Cycle Progression

Cyclins and proto-oncogenes including c-myc have been implicated in eukaryotic cell cycle control. The role of cyclins in steroidal regulation of cell proliferation is unknown, but a role for c-myc has been suggested. This study investigated the relationship between regulation of T-47D breast cancer cell cycle progression, particularly by steroids and their antagonists, and changes in the levels of expression of these genes. Sequential induction of cyclins D1 (early G1 phase), D3, E, A (late G1-early S phase), and B1 (G2 phase) was observed following insulin stimulation of cell cycle progression in serum-free medium. Transient acceleration of G1-phase cells by progestin was also accompanied by rapid induction of cyclin D1, apparent within 2 h. This early induction of cyclin D1 and the ability of delayed administration of antiprogestin to antagonize progestin-induced increases in both cyclin D1 mRNA and the proportion of cells in S phase support a central role for cyclin D1 in mediating the mitogenic response in T-47D cells. Compatible with this hypothesis, antiestrogen treatment reduced the expression of cyclin D1 approximately 8 h before changes in cell cycle phase distribution accompanying growth inhibition. In the absence of progestin, antiprogestin treatment inhibited T-47D cell cycle progression but in contrast did not decrease cyclin D1 expression. Thus, changes in cyclin D1 gene expression are often, but not invariably, associated with changes in the rate of T-47D breast cancer cell cycle progression. However, both antiestrogen and antiprogestin depleted c-myc mRNA by > 80% within 2 h. These data suggest the involvement of both cyclin D1 and c-myc in the steroidal control of breast cancer cell cycle progression.

scholarly journals Hormonal Control of Breast Cancer Cell Cycle Progression

1994 ◽  
pp. 15-25 ◽  
Author(s):  
Robert L. Sutherland ◽  
Jenny A. Hamilton ◽  
Colin K. W. Watts ◽  
Elizabeth A. Musgrove
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Cycle Progression ◽  
Hormonal Control ◽  
Cycle Progression

Growth factor, steroid, and steroid antagonist regulation of cyclin gene expression associated with changes in T-47D human breast cancer cell cycle progression

1993 ◽  
Vol 13 (6) ◽  
pp. 3577-3587
Author(s):  
E A Musgrove ◽  
J A Hamilton ◽  
C S Lee ◽  
K J Sweeney ◽  
C K Watts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Cycle Progression ◽  
S Phase ◽  
G1 Phase ◽  
Cycle Progression

Cyclins and proto-oncogenes including c-myc have been implicated in eukaryotic cell cycle control. The role of cyclins in steroidal regulation of cell proliferation is unknown, but a role for c-myc has been suggested. This study investigated the relationship between regulation of T-47D breast cancer cell cycle progression, particularly by steroids and their antagonists, and changes in the levels of expression of these genes. Sequential induction of cyclins D1 (early G1 phase), D3, E, A (late G1-early S phase), and B1 (G2 phase) was observed following insulin stimulation of cell cycle progression in serum-free medium. Transient acceleration of G1-phase cells by progestin was also accompanied by rapid induction of cyclin D1, apparent within 2 h. This early induction of cyclin D1 and the ability of delayed administration of antiprogestin to antagonize progestin-induced increases in both cyclin D1 mRNA and the proportion of cells in S phase support a central role for cyclin D1 in mediating the mitogenic response in T-47D cells. Compatible with this hypothesis, antiestrogen treatment reduced the expression of cyclin D1 approximately 8 h before changes in cell cycle phase distribution accompanying growth inhibition. In the absence of progestin, antiprogestin treatment inhibited T-47D cell cycle progression but in contrast did not decrease cyclin D1 expression. Thus, changes in cyclin D1 gene expression are often, but not invariably, associated with changes in the rate of T-47D breast cancer cell cycle progression. However, both antiestrogen and antiprogestin depleted c-myc mRNA by > 80% within 2 h. These data suggest the involvement of both cyclin D1 and c-myc in the steroidal control of breast cancer cell cycle progression.

scholarly journals LMO4 is an essential mediator of ErbB2/HER2/Neu-induced breast cancer cell cycle progression

Oncogene ◽  
2009 ◽  
Vol 28 (41) ◽  
pp. 3608-3618 ◽  
Author(s):  
M E Montañez-Wiscovich ◽  
D D Seachrist ◽  
M D Landis ◽  
J Visvader ◽  
B Andersen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Cycle Progression ◽  
Cycle Progression
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