Gene delivery of cyclin-dependent kinase inhibitors p21 Waf1 and p27 Kip1 suppresses proliferation of MCF-7 breast cancer cells in vitro

Jiang, Dandan; Wang, Xingang; Liu, Xiangping; Li, Funian

doi:10.1007/s12282-012-0438-y

Cited by 15 publications

(14 citation statements)

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“…This is further supported by our data, which show a down regulation of other significant cell cycle-associated genes, including Ccne1, Cdk2, E2f5, and Rbl1, in parous ALDH positive MECs. p21 is known to be suppressed in many human cancers; it was recently shown in a preclinical study that the up regulation of p21 leads to an anti-proliferative effect in breast cancer cell lines with cell cycle arrest in G1 phase [46]. Further, our cell proliferation data also indicates a higher proliferation rate in virgin ALDH positive MECs.…”

Section: Discussionsupporting

confidence: 61%

microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy

et al. 2014

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BackgroundmicroRNAs have recently succeeded in grabbing the center stage in cancer research for their potential to regulate vital cellular process like cell cycle, stem cell renewal and epithelial mesenchymal transition. Breast cancer is the second most leading cause of cancer related mortality in women. The main reason for mortality is chemoresistance and metastasis for which remnant stem cells are believed to be the cause. One of the natural ways to reduce the risk of breast cancer in women is early pregnancy. Unraveling the mechanism behind it would add to our knowledge and help in evolving newer paradigms for breast cancer prevention.The current study deals with investigating transcriptomic differences in putative stem cells in mammary epithelial cell population (MECs) in terms of genes and microRNAs. In silico tools were used to identify potential mechanisms. ALDH positive MECs represent a putative stem cell population in the mammary gland.MethodsMECs were extracted from the mammary gland of virgin and parous (one time pregnant) rats. ALDH positive MECs were sorted and used for transcriptional and translational analysis for genes and microRNAs. In silico analysis for target prediction and networking was performed through online portals of Target Scan and Metacore.ResultsA total of 35 and 49 genes and microRNAs respectively were found to be differentially expressed within the two groups. Among the important genes were Lifr, Acvr1c, and Pparγ which were found to be targeted by microRNAs in our dataset like miR-143, miR-30, miR-140, miR-27b, miR-125a, miR-128ab, miR-342, miR-26ab, miR-181, miR-150, miR-23ab and miR-425. In silico data mining and networking also demonstrates that genes and microRNA interaction can have profound effects on stem cell renewal, cell cycle dynamics and EMT processes of the MEC population.ConclusionsOur data clearly shows that certain microRNAs play crucial role in the regulation of ALDH positive MECs and favor an anti-carcinogenic environment in the post-partum gland. Some of the potential interplaying mechanisms in the ALDH positive MEC population identified through this study are p21, Lifr and Pparγ mediated cell cycle regulation, regulation of metastasis and expansion of stem cell pool respectively.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-644) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 61%

microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy

et al. 2014

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“…In addition, levels of p21 (cyclin-dependent kinase inhibitor 1 (WAF1)) and p27 (kinesin-like protein (KIP1)) proteins increased, as did apoptosis regulator BCL-2-like protein 4 (BAX) expression, whereas apoptosis regulator B-cell lymphoma 2 (BCL2) expression was reduced (69). p21 and p27 are inhibitors of cyclin-dependent kinases, hence they are involved in cellcycle control (70) and appear to suppress MCG-7 cell proliferation in vitro (71). BAX is a pro-apoptotic member of the BCL2 family and a downstream target gene of p53 that mediates p53-dependent apoptosis (72).…”

Section: Hdac Inhibitors As Anti-breast Cancer Agentsmentioning

confidence: 99%

Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer

et al. 2017

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Abstract. With a lifetime risk estimated to be one in eight in industrialized countriesBreast cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related death among women worldwide. According to the American Cancer Society about 12% U.S. women will develop breast cancer during their lifetime. Moreover, in 2015, about 2,300 men were diagnosed with breast cancer and 440 died from the disease (1, 2).In approximately 90% of breast cancer cases, estrogen receptor α (ERα), progesterone receptor (PR), or the human epidermal growth factor receptor2 (HER2/ERBB2) protooncogenic receptor are expressed. In many of these patients, treatment with anti-estrogens (e.g. aromatase inhibitors, tamoxifen, fulvestrant) and HER2-targeted agents has improved their survival significantly (3, 4). However, despite 35

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“…Therefore, cell cycle regulation is vital for cell proliferation and tumorigenesis. The cell cycle involves cell cycle proteins (cyclins) and cyclin-dependent kinase (CDK) enzymes that positively regulate cell cycle progression, while cyclin-dependent kinase inhibitor (CKI) plays a negative regulatory role (Stivala et al, 2012;Jiang et al, 2014). Interaction between the two components controls the cell cycle process.…”

Section: Introductionmentioning

confidence: 99%

S-phase kinase-associated protein 2 expression interference inhibits breast cancer cell proliferation

Sun

2015

Genet. Mol. Res.

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ABSTRACT. We investigated the expression of S-phase kinaseassociated protein 2 (SKP2) in breast cancer tissues, and the effects of SKP2-specific small interfering RNA (siRNA) interference on breast cancer cell proliferation. Thirty subjects provided breast cancer tissue samples and 18 subjects provided normal breast specimens for this study. The expression of SKP2 in breast cancer patient tissues and normal breast tissues was detected by western blotting analysis and reverse transcription-polymerase chain reaction. SKP2-specific siRNA was used to decrease SKP2 expression in breast cancer cell line MDA-MB-231. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell proliferation. SKP2 expression in breast cancer tissues was significantly higher than in normal breast tissues (P < 0.05). Two pairs of siRNA specific to SKP2 were required to downregulate SKP2 expression in the breast cancer cell line MDA-MB-231. The MTT assay showed that MDA-MB-231 growth significantly slowed after SKP2 interference. Patients with breast cancer have an increased 9245 SKP2 expression and breast cancer cell proliferation ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 9244-9252 (2015) SKP2 level. Interference in SKP2 gene expression can inhibit breast cancer cell growth, suggesting that SKP2 is potentially a new target for breast cancer therapy.

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Gene delivery of cyclin-dependent kinase inhibitors p21 Waf1 and p27 Kip1 suppresses proliferation of MCF-7 breast cancer cells in vitro

Cited by 15 publications

References 17 publications

microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy

microRNA alterations in ALDH positive mammary epithelial cells: a crucial contributing factor towards breast cancer risk reduction in case of early pregnancy

Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer

S-phase kinase-associated protein 2 expression interference inhibits breast cancer cell proliferation

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