Silencing CDK4 radiosensitizes breast cancer cells by promoting apoptosis

Hagen, Katie R.; Zeng, Xianyi; Lee, Mi Young; Kahn, Shannon; Pitner, Mary Kathryn; Zaky, Sandra S.; Liu, Yuan; O’Regan, Ruth; Deng, Xingming; Saavedra, Harold I.

doi:10.1186/1747-1028-8-10

Cited by 37 publications

(29 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three different cyclins as D1, D2, and D3 are identified in mammalian cells. Actually the cyclins (mainly cyclin D1) are involved in G1/S cell transition . It has been identified that the cyclin D1 plays two opposing roles in cell proliferation and/or the cell cycle arrest .…”

Section: Introductionmentioning

confidence: 99%

Roles of p21, p53, cyclin D1, CDK‐4, estrogen receptor α in aflatoxin B1‐induced cytotoxicity in testicular tissue of mice

Zamir-Nasta

Razi

Hasanzadeh

et al. 2017

Environmental Toxicology

View full text Add to dashboard Cite

This study was done in order to investigate time-dependent effect of AFB1 on expression of genes involving in cell cycle check point machinery at G, S, and M phases. For this purpose, 24 mature male Swiss albino mice were randomly divided into control and test groups. The animals in test group subdivided into three groups, which received the AFB1 at a daily dose of 20 µg/kg body weight, through intraperitoneal (i.p.) route, for 7, 14, and 21 days. The p21, p53, cyclin D1, CDK4, and ERα expressions at both mRNA and protein level were analyzed by using reverse transcription PCR (RT-PCR) and immunohistochemistry, respectively. Moreover, the tubular differentiation (TDI) and spermiogenesis (SPI) indices were analyzed. Finally, the testicular DNA fragmentation was assessed by using DNA Ladder test. Observations revealed that the AFB1 remarkably (P < .05) reduced cyclin D1, Cdk4, and ERα expression at both mRNA and protein levels. Up-regulated p21 and p53 expression was revealed in AFB1-received animals, which developed time dependently. Histological examinations exhibited a significant reduction in TDI and SPI indices. Finally, the AFB1 resulted in severe DNA fragmentation. Our data showed that the AFB1 by down-regulating the cyclin D1, Cdk4, and ERα expression adversely affects cyclin D1/Cdk4 and cyclin D1/ERα interactions. Moreover, the AFB1-induced overexpression of p21 (as a kinase inhibitor), in turn results in cell cycle arrest via inhibiting the Cdk4 interaction with cyclin D1. Finally, the AFB1-induced DNA damage triggers the p53-dependent apoptosis pathway independent to p21 overexpression.

show abstract

Section: Introductionmentioning

confidence: 99%

Roles of p21, p53, cyclin D1, CDK‐4, estrogen receptor α in aflatoxin B1‐induced cytotoxicity in testicular tissue of mice

Zamir-Nasta

Razi

Hasanzadeh

et al. 2017

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…Western blotting was performed according to our published protocols (59,61,62 Live-cell image analysis. HCC1954 cells transduced with pLKO.1, shE2F3, or shE2F3; GFP-Nek2 (1 ϫ 10 4 to 2 ϫ 10 4 cells/well) were plated on an eight-chambered #1.5 German coverglass system (155409; Thermo Scientific).…”

Section: Methodsmentioning

confidence: 99%

E2F Activators Signal and Maintain Centrosome Amplification in Breast Cancer Cells

Lee

Moreno

Saavedra

2014

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

bCentrosomes ensure accurate chromosome segregation by directing spindle bipolarity. Loss of centrosome regulation results in centrosome amplification, multipolar mitosis and aneuploidy. Since centrosome amplification is common in premalignant lesions and breast tumors, it is proposed to play a central role in breast tumorigenesis, a hypothesis that remains to be tested. The coordination between the cell and centrosome cycles is of paramount importance to maintain normal centrosome numbers, and the E2Fs may be responsible for regulating these cycles. However, the role of E2F activators in centrosome amplification is unclear. Because E2Fs are deregulated in Her2؉ cells displaying centrosome amplification, we addressed whether they signal this abnormal process. Knockdown of E2F1 or E2F3 in Her2 ؉ cells decreased centrosome amplification without significantly affecting cell cycle progression, whereas the overexpression of E2F1, E2F2, or E2F3 increased centrosome amplification in MCF10A mammary epithelial cells. Our results revealed that E2Fs affect the expression of proteins, including Nek2 and Plk4, known to influence the cell/centrosome cycles and mitosis. Downregulation of E2F3 resulted in cell death and delays/blocks in cytokinesis, which was reversed by Nek2 overexpression. Nek2 overexpression enhanced centrosome amplification in Her2؉ breast cancer cells silenced for E2F3, revealing a role for the E2F activators in maintaining centrosome amplification in part through Nek2.

show abstract

“…An in vitro study of breast cancer cells found that cell lines which were knocked down for CDK 4 had significant radiosensitization (36). A CDK 4/6 inhibitor also allowed for radio-sensitization of MDA-MB-468 cells.…”

Section: Cdk 4/6 Inhibitors As a Radio-sensitizermentioning

confidence: 98%

Cyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Breast Cancer: A Review of Preclinical and Clinical Data

Vidula

Rugo

2016

Clinical Breast Cancer

View full text Add to dashboard Cite

Silencing CDK4 radiosensitizes breast cancer cells by promoting apoptosis

Cited by 37 publications

References 102 publications

Roles of p21, p53, cyclin D1, CDK‐4, estrogen receptor α in aflatoxin B1‐induced cytotoxicity in testicular tissue of mice

Roles of p21, p53, cyclin D1, CDK‐4, estrogen receptor α in aflatoxin B1‐induced cytotoxicity in testicular tissue of mice

E2F Activators Signal and Maintain Centrosome Amplification in Breast Cancer Cells

Cyclin-Dependent Kinase 4/6 Inhibitors for the Treatment of Breast Cancer: A Review of Preclinical and Clinical Data

Contact Info

Product

Resources

About