Increased cell growth and tumorigenicity in human prostate LNCaP cells by overexpression to cyclin D1

Chen, Yi‐An; Martínez, Luis; LaCava, Margaret; Coghlan, Lezlee G; Conti, Claudio J.

doi:10.1038/sj.onc.1201719

Cited by 85 publications

(58 citation statements)

References 31 publications

(54 reference statements)

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“…Cyclin D1 mRNA levels are increased in both primary prostate cancer samples (Han et al, 1998) and androgenindependent bone metastasis (Drobnjak et al, 2000). Furthermore, increased expression of cyclin D1 in LNCaP enhanced cell growth and tumorigenicity (Chen et al, 1998;Perry et al, 1998). Therefore, inhibition of cyclin D1 may be an interesting molecular target to control tumor proliferation (Zhang et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level

et al. 2008

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Metformin is a widely used antidiabetic agent, which regulates glucose homeostasis through inhibition of liver glucose production and an increase in muscle glucose uptake. Recent studies suggest that metformin may reduce the risk of cancer, but its mode of action in cancer remains not elucidated. We investigated the effect of metformin on human prostate cancer cell proliferation in vitro and in vivo. Metformin inhibited the proliferation of DU145, PC-3 and LNCaP cancer cells with a 50% decrease of cell viability and had a modest effect on normal prostate epithelial cell line P69. Metformin did not induce apoptosis but blocked cell cycle in G 0 /G 1 . This blockade was accompanied by a strong decrease of cyclin D1 protein level, pRb phosphorylation and an increase in p27 kip protein expression. Metformin activated the AMP kinase pathway, a fuel sensor signaling pathway. However, inhibition of the AMPK pathway using siRNA against the two catalytic subunits of AMPK did not prevent the antiproliferative effect of metformin in prostate cancer cells. Importantly, oral and intraperitoneal treatment with metformin led to a 50 and 35% reduction of tumor growth, respectively, in mice bearing xenografts of LNCaP. Similar, to the in vitro study, metformin led to a strong reduction of cyclin D1 protein level in tumors providing evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent epidemiological studies.

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Section: Discussionmentioning

confidence: 99%

The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level

et al. 2008

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“…Excess of MMPs stimulates tumour invasion and metastasis (Kugler, 1999;Sato et al, 1992). Cyclin D1 initiates the G1-S phase progression (Chen et al, 1998). Oestrogens are found to induce nuclear localization of Cyclin D1 in endometrial cells, resulting in increased cell proliferation (Tong and Pollard, 1999).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method

et al. 2000

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SummaryThe recently developed cDNA expression array technique can be used to generate gene-expression fingerprints of tumour specimens. To gain insight into molecular mechanisms involved in the development and progression of cancer, this cDNA expression array technique could be a useful tool, however, no established methods for interpreting the results are yet available. We used the Atlas cancer cDNA expression array (Clontech, USA) for analysing total RNA isolated from four human endometrial carcinoma samples (two cell-lines and two tissue samples), one benign endometrial tissue sample and a human breast cancer cell-line, in order to develop a method for analysing the array data. The obtained gene-expression profiles were highly reproducible. XY-scatterplots and regression analysis of the logarithmic transformed data provided a practical method to analyse the data without the need of preceding normalization. Three genes (Decorin, TIMP3 and Cyclin D1) were identified to be differentially expressed between the benign endometrial tissue sample and the endometrial carcinoma samples (tissue and cell-lines). These three genes may potentially be involved in cancer progression. A higher degree of similarity in geneexpression profile was found between the endometrial samples (tissue and cell-lines) than between the endometrial samples and the breast cancer cell-line, which is indicative for an endometrial tissue-specific gene-expression profile.

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“…Cyclin D1, whose expression is increased in prostate cancer cell lines and clinical tumors, is causally related to tumorigenesis (38). In vivo cyclin D1 overexpression in LNCaP cells yielded faster tumor growth and insensitivity to castration (39). It was also shown that cyclin D1 expression correlates with metastatic spread of prostate cancer to bone (40).…”

Section: Discussionmentioning

confidence: 99%

Akacid-medical-formulation, a novel biocidal oligoguanidine with antitumor activity reduces S-phase in prostate cancer cell lines through the Erk 1/2 mitogen-activated protein kinase pathway

Neuwirt

Müller²,

Cavarretta³

et al. 2006

Int J Oncol

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Abstract. Oligomeric guanidines are highly efficient biocides against a broad spectrum of microorganisms. However, their antitumor effects have not been studied so far. We investigated an antiproliferative effect of Akacid-medical-formulation (AMF), a member of the oligoguanidine family of biocides, against solid cancer cell lines and primary cells by measuring [3 H]-thymidine incorporation. Additionally, we examined cell cycle distribution in two AMF-sensitive prostate cancer cell lines (DU-145, LNCaP) using flow cytometry. Finally, the influence of AMF on cell cycle regulatory molecules and intracellular kinase cascade-related signaling molecules was assessed. We found that AMF has variable antiproliferative effects on all tested cells. In DU-145 and LNCaP cells, flow cytometric studies showed a reduction of S-phase with a maximum extent of 24 and 58%, respectively. This was associated with a decrease in expression of cyclin D1, cyclindependent kinases 2 and 4, while having varying effects on expression of cyclin E and p27. Additionally, reduced phosphorylation of Erk1 and Erk2 was found, whereas expression of phospho-Akt1 remained unchanged. Herein we report for the first time that AMF exerts potent antiproliferative activity against various malignant cell lines, including those of prostate. We therefore recommend further investigation of the anticancer activity of this biocidal oliguanidine.

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Increased cell growth and tumorigenicity in human prostate LNCaP cells by overexpression to cyclin D1

Cited by 85 publications

References 31 publications

The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level

The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level

Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method

Akacid-medical-formulation, a novel biocidal oligoguanidine with antitumor activity reduces S-phase in prostate cancer cell lines through the Erk 1/2 mitogen-activated protein kinase pathway

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