Ki-67 and PCNA expression in prostate cancer and benign prostatic hyperplasia

Zhong, Weide; Peng, Jinyu; He, Hao; Wu, Dinglan; Han, Zhengxue; Bi, Xiangjun; Dai, Qi-Shan

doi:10.25011/cim.v31i1.3136

Cited by 90 publications

(84 citation statements)

References 15 publications

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“…Since survivin was reported to be a downstream regulator in the ID1/PI3K/Akt/NF-κB/survivin signaling pathway for endothelial progenitor cell proliferation, and CRC tumor growth and malignant metastasis (25,26), the fact that ID1 knockdown induced a decrease in survivin expression, may indicate that activation of survivin is a consequence of the expression of ID1 in CRC cell lines. It has been suggested that PCNA is a proliferation marker of tumors and is critical for DNA synthesis (27). We showed that ID1 knockdown decreased PCNA expression at both the mRNA and protein levels.…”

Section: Discussionmentioning

confidence: 57%

Inhibitor of DNA-binding protein 1 knockdown arrests the growth of colorectal cancer cells and suppresses hepatic metastasis in vivo

et al. 2014

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Abstract. Inhibitor of DNA-binding protein 1 (ID1) is commonly abnormally overexpressed in colorectal cancer (CRC); yet, the functional significance of ID1 in the growth and invasive properties of CRC cells remains largely unclear. The present study investigated the effects of ID1 downregulation on the cell growth and metastatic features of CRC. Using lentiviral shRNA infection, stable ID1-knockdown (KD) HCT116 and SW620 cells, human metastatic CRC cell lines, were created. In vitro, the migration/invasion capacity of the ID1-KD CRC cells was assessed by a wound healing assay. The activities of MMP2 and MMP-9 were measured by gelatin zymography. The expression of CXC chemokine receptor 4 (CXCR4), PCNA and survivin were determined by immunoblot analysis and qRT-PCR. The effects of ID1 knockdown on tumor growth and hepatic metastasis were demonstrated by a xenograft study in mice. The results showed evident decreases in proliferation, migration and invasion and an increased apoptosis rate in the ID1-KD CRC cells. Similarly, ID1 knockdown significantly decreased mRNA and protein levels of PCNA, survivin, CXCR4, MMP2 and MMP9. Overexpression of CXCR4 antagonized the negative effect on the migration and invasion abilities of the ID1-KD cells. As compared with the control, ID1 knockdown prevented tumor growth and profoundly suppressed hepatic metastasis in vivo. The present study demonstrated the significance of ID1 in colon cancer progression, and its effect on tumor invasiveness and metastatic properties may be partly dependent on CXCR4.

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Section: Discussionmentioning

confidence: 57%

Inhibitor of DNA-binding protein 1 knockdown arrests the growth of colorectal cancer cells and suppresses hepatic metastasis in vivo

et al. 2014

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“…PCNA expression is significantly elevated in patients with BPH or prostate cancer, and the extent of cell proliferation is related to the clinical grade of prostate cancer. 37) Animals with experimentally induced BPH also have significantly increased prostatic PCNA expression. 38,39) We found that rats with BPH that were given QI treatment had significantly reduced expression of PCNA and cyclin D1, as well as fewer PCNA-positive cells.…”

Section: Discussionmentioning

confidence: 99%

<i>Quisqualis indica</i> Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis

Wijerathne

Park

Jeong

et al. 2017

Biological & Pharmaceutical Bulletin

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Quisqualis indica (QI) has been used for treating disorders such as stomach pain, constipation, and digestion problem. This study was aimed to evaluate the therapeutic efficacy of QI extract on treating benign prostatic hyperplasia (BPH) in LNCaP human prostate cancer cell line and a testosterone-induced BPH rat model. LNCaP cells were treated with QI plus testosterone propionate (TP), and androgen receptor (AR) and prostate specific antigen (PSA) expression levels were assessed by Western blotting. To induce BPH, the rats were subjected to a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks. The rats in treatment group were orally gavaged with QI (150 mg/kg) together with the TP injection. In-vitro studies showed that TPinduced increases in AR and PSA expression in LNCaP cells were reduced by QI treatment. In BPH-model rats, the prostate weight, testosterone in serum, dihydrotestosterone (DHT) concentration and 5α-reductase type 2 mRNA expression in prostate tissue were significantly reduced following the treatment with QI. TPinduced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were significantly attenuated in QI-treated rats. In addition, QI induced apoptosis by up-regulating caspase-3 and -9 activity and decreasing the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio in prostate tissues of BPH rats. Further investigation showed that TP-induced activation of AKT and glycogen synthase kinase 3β (GSK3β) was reduced by QI administration. Therefore, our findings suggest that QI attenuates the BPH state in rats through anti-proliferative and pro-apoptotic activities and might be useful in the clinical treatment of BPH.Key words benign prostatic hyperplasia; dihydrotestosterone; Quisqualis indica; testosterone Benign prostatic hyperplasia (BPH) is a common urogenital disorder that affects up to 85% of males who are over 50 years-old. 1) BPH is characterized by the increased proliferation of epithelial and stromal cells of the prostate.2) BPH generally causes lower urinary tract symptoms (LUTS), such as incomplete bladder emptying, bladder obstruction, bloody urination, and frequent urination.3)The etiology of BPH is not entirely clear. However, the development and incidence of BPH are associated with dysregulation of androgens, and with increased proliferation and decreased apoptosis of cells in the prostate gland.4-9) Testosterone and dihydrotestosterone (DHT) have key roles in the development and growth of the entire male genital tract, and they stimulate differentiation of the prostate gland. 10,11) The adrenal glands and testes synthesize testosterone, and prostatic 5α-reductase type 2 converts it to DHT. 12) DHT then binds to the androgen receptor (AR), which is transported to the nucleus, where it regulates genes important for prostate growth and differentiation. 4) BPH development and progression are associated with activation of the AKT pathway, a major growth factor-mediated signal transduction pathways. 6)Over-stimulation of the ...

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“…PCNA gene deregulation and post-translational modulation are hallmarks of malignant cells. Tumor cells, regardless of their origins, express higher levels of PCNA (Celis and Olsen, 1994;Kallakury et al, 1999;Kimos et al, 2004;Malkas et al, 2006;Miyamoto et al, 2006;Naryzhny and Lee, 2007;Eltz et al, 2008;Naryzhny, 2008;Stuart-Harris et al, 2008;Zhong et al, 2008;Stoimenov and Helleday, 2009). Expression levels of PCNA correlate positively with other pathological indices in prostate cancer (Mulligan et al, 1997) and can serve as an independent prognosis marker (Miyamoto et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Small-Molecule Targeting of Proliferating Cell Nuclear Antigen Chromatin Association Inhibits Tumor Cell Growth

Tan¹,

Wortman²,

Dillehay³

et al. 2012

Mol Pharmacol

120

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Proliferating cell nuclear antigen (PCNA), a potential anticancer target, forms a homotrimer and is required for DNA replication and numerous other cellular processes. The purpose of this study was to identify novel small molecules that modulate PCNA activity to affect tumor cell proliferation. An in silico screen of a compound library against a crystal structure of PCNA and a subsequent structural similarity search of the ZINC chemical database were carried out to derive relevant docking partners. Nine compounds, termed PCNA inhibitors (PCNA-Is), were selected for further characterization. PCNA-I1 selectively bound to PCNA trimers with a dissociation constant (K d ) of ϳ0.2 to 0.4 M. PCNA-Is promoted the formation of SDSrefractory PCNA trimers. PCNA-I1 dose-and time-dependently reduced the chromatin-associated PCNA in cells. Consistent with its effects on PCNA trimer stabilization, PCNA-I1 inhibited the growth of tumor cells of various tissue types with an IC 50 of ϳ0.2 M, whereas it affected the growth of nontransformed cells at significantly higher concentrations (IC 50 , ϳ1.6 M). Moreover, uptake of BrdU was dose-dependently reduced in cells treated with PCNA-I1. Mechanistically the PCNA-Is mimicked the effect of PCNA knockdown by siRNA, inducing cancer cell arrest at both the S and G 2 /M phases. Thus, we have identified a class of compounds that can directly bind to PCNA, stabilize PCNA trimers, reduce PCNA association with chromatin, and inhibit tumor cell growth by inducing a cell cycle arrest. They are valuable tools in studying PCNA function and may be useful for future PCNA-targeted cancer therapy.

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Ki-67 and PCNA expression in prostate cancer and benign prostatic hyperplasia

Cited by 90 publications

References 15 publications

Inhibitor of DNA-binding protein 1 knockdown arrests the growth of colorectal cancer cells and suppresses hepatic metastasis in vivo

Inhibitor of DNA-binding protein 1 knockdown arrests the growth of colorectal cancer cells and suppresses hepatic metastasis in vivo

<i>Quisqualis indica</i> Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis

Small-Molecule Targeting of Proliferating Cell Nuclear Antigen Chromatin Association Inhibits Tumor Cell Growth

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