Widely used prostate carcinoma cell lines share common origins

Bokhoven, Adrie van; Varella‐Garcia, Marileila; Korch, Christopher; Hessels, Daphne; Miller, Gary J.

doi:10.1002/pros.1045.abs

Cited by 23 publications

(36 citation statements)

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“…29 At least five of the prostate cancer cell lines we examined harbor p53 mutations ( Du145, JCA -1, PC -3, PPC -1, TsuPr1). 37 Only LNCaP and PrEC have confirmed wildtype p53. 37 Therefore, the synergistic effect observed between doxorubicin and TRAIL did not require functional p53.…”

Section: Discussionmentioning

confidence: 98%

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Resistance of prostate cancer cells to soluble TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) can be overcome by doxorubicin or adenoviral delivery of full-length TRAIL

Voelkel‐Johnson

King

Norris³

2002

Cancer Gene Ther

103

100

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Tumor necrosis factor -related apoptosis -inducing ligand ( TRAIL / Apo2L ) has been shown to induce apoptosis in malignant cells without harming normal cells. To determine the antitumor potential of TRAIL against prostate cells, we undertook a comprehensive study that included eight prostate cancer cells lines ( CWR22Rv1, Du145, DuPro, JCA -1, LNCaP, PC -3, PPC -1, and TsuPr1 ) and primary cultures of normal prostate epithelial cells ( PrEC ). Cells were tested for susceptibility to soluble TRAIL in the presence or absence of the chemotherapeutic agent doxorubicin. TRAIL was also delivered by an adenoviral vector. Our results reveal that Du145, DuPro, LNCap, TsuPr1, and PrEC were resistant to 100 ng / mL TRAIL. JCA -1 and PPC -1 were slightly sensitive ( 20% killing ) and PC -3 and CWR22Rv1 exhibited the highest sensitivity to TRAIL ( 30% and 50% killing, respectively ). The combination of 10 ng / mL TRAIL with doxorubicin resulted in 60 -80% cytotoxicity in seven of eight prostate cancer cells. TRAIL -mediated apoptosis involved cleavage of Bid, caspase -3, and PARP, and required caspase -8 and -9 activity. Full -length TRAIL delivered by an adenoviral vector ( AdTRAIL -IRES -GFP ) killed prostate cancer cell lines and PrEC without requisite doxorubicin cotreatment. Therefore, expression of the transgene from a tissue -specific promotor would make gene therapy with AdTRAIL -IRES -GFP a possibility.

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Section: Discussionmentioning

confidence: 98%

“…37 Only LNCaP and PrEC have confirmed wildtype p53. 37 Therefore, the synergistic effect observed between doxorubicin and TRAIL did not require functional p53. Du145, which was most refractory to the combined treatment, does not express the proapoptotic protein Bax.…”

Section: Discussionmentioning

confidence: 98%

Resistance of prostate cancer cells to soluble TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) can be overcome by doxorubicin or adenoviral delivery of full-length TRAIL

Voelkel‐Johnson

King

Norris³

2002

Cancer Gene Ther

103

100

View full text Add to dashboard Cite

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“…This could possibly be explained by the fact that LNCaP cells are known to be a cell line expressing prostatic markers and being hormone sensitive, whereas PC3 and TSU-Pr1 cells are less differentiated (Kaighn et al, 1979;Horoszewicz et al, 1983;Webber et al, 1996). PC3 and TSU-Pr1 cells carry molecular alterations such as a mutated p53 and the origin of TSU-Pr1 cells is discussed controversially (Iizumi et al, 1987;van-Bokhoven et al, 2001). On the chicken egg membrane, PC3 tumours seemed to be more sensitive especially when treated with tributyrin.…”

Section: Discussionmentioning

confidence: 99%

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

et al. 2004

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Histone deacetylase inhibitors (HDACs) are known to exhibit antiproliferative effects on various carcinoma cells. In this study, the in vivo efficiency of two HDACs, sodium butyrate and tributyrin, on prostate cancer growth inhibition were investigated. To gain an insight into the possible underlying pathways, cell culture experiments were performed focusing on the expression of p21, Rb and cmyc. For in vivo testing, prostate cancer cell lines (PC3 and TSU-Pr1) were seeded on the chorioallantois membrane (CAM) and implanted in a xenograft model using nude mice. Standard Western blot analysis was performed for protein expression of p21, Rb and c-myc in HDAC-treated vs untreated prostate cancer cells. Both sodium butyrate and tributyrin had a considerable treatment effect on microtumours on the chicken egg at already very low concentrations of 0.1 mM. Tributyrin-treated tumours showed the strongest effect with 38% apoptotic nuclei in the prostate cancer cell line PC3. In the mouse model, there was almost no difference between sodium butyrate and tributyrin. In untreated animals the tumours were almost double the size 4 weeks after implantation. Tumours of the treatment groups had a significantly lower percentage of Ki-67-positive-stained nuclei. As demonstrated by Western blot analysis, these effects seem to be independent of p53 status and a pathway via p21 -Rb -c-myc is possibly involved. In this study we have demonstrated a substantial in vivo treatment effect, which can be induced by the application of sodium butyrate or the orally applicable tributyrin in human prostate cancer. The given results may provide the rationale to apply these drugs in well-controlled clinical trials in patients being at high risk of recurrence after specific therapy or in patients with locally or distant advanced prostate cancer.

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“…[54][55][56][57] They consisted of a transition C-T in codon 223 of exon 6, generating the missense mutation P223L and a transversion G-T in codon 274 of exon 8, resulting in the missense mutation V274F.…”

Section: Klf6 Andmentioning

confidence: 99%

KLF6 and TP53 mutations are a rare event in prostate cancer: distinguishing between Taq polymerase artifacts and true mutations

et al. 2008

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Krü ppel-like factor 6 (KLF6) has been reported to act as a tumor suppressor gene involved in the regulation of the cell cycle by activating p21 in a p53-independent manner. Many studies suggest that KLF6 is inactivated by allelic loss and somatic mutation. However, there is a high variability in the reported frequency of mutations (from 1 to 55%). TP53 also regulates the cell cycle through the activation of p21. In prostate cancer, the reported frequency of TP53 mutations ranges from 3 to 42%. In all these reports, there is a considerable degree of methodological heterogeneity. Our aim was to determine the frequency of KLF6 and TP53 mutations in a welldefined group of prostate tumors with different stages and Gleason grades. The four exons of KLF6 and exons 4-9 of TP53 were studied in 103 cases, including 90 formalin-fixed, paraffin-embedded (FFPE) and 13 frozen samples. All tumors were analyzed through PCR and direct sequencing. All changes found were confirmed by a second independent PCR and sequencing reaction. For KLF6, mutation (E227G) was only detected in one tumor (1%) and for TP53, three different mutations (L130H, H214R, and Y234C) were detected in five tumors (5%). This low mutation index is in keeping with recent papers on the subject. Our study strongly supports the notion that KLF6 and TP53 mutations are not frequent events in prostate cancer. When using FFPE tissues, it is mandatory to perform at least two independent rounds of PCR and sequencing to confirm mutations and exclude Taq polymerase-induced artifacts. Two of these genes are Krü ppel-like factor 6 (KLF6) and TP53.KLF6 is a transcription factor that interacts with DNA through three zinc-fingers in its COOHterminal domain. KLF6 belongs to the KLF family, a family that is broadly involved in cell differentiation, development, growth-related signal transduction, cell proliferation, apoptosis, and angiogenesis. 5 It has been suggested that KLF6 could be involved in the regulation of the cell cycle by activating p21 in a p53-independent manner. 6 This has been proven in several in vitro 5 and in vivo assays. 7 KLF6 is believed to regulate cancer development and progression through the downregulation of the c-Jun oncoprotein 8 and the activation of E-cadherin. 9 The reported frequency of KLF6 mutations in different types of human cancer varies in the different published studies. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] In prostate cancer, four studies have analyzed the frequency of KLF6 mutations. 6,[30][31][32] In the first published study, Narla et al 6 showed a very high frequency, 55%, whereas in the following study, Chen et al 30 obtained a lower frequency, around 15%. The results of two recent reports provided frequencies of 0 and 1%. 31,32 It should be noted that there were considerable

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Widely used prostate carcinoma cell lines share common origins

Cited by 23 publications

References 0 publications

Resistance of prostate cancer cells to soluble TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) can be overcome by doxorubicin or adenoviral delivery of full-length TRAIL

Resistance of prostate cancer cells to soluble TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) can be overcome by doxorubicin or adenoviral delivery of full-length TRAIL

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

KLF6 and TP53 mutations are a rare event in prostate cancer: distinguishing between Taq polymerase artifacts and true mutations

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