Heterogeneity of molecular targets on clonal cancer lines derived from a novel hormone‐refractory prostate cancer tumor system

Freedland, Stephen J.; Pantuck, Allan J.; Paik, Seung Hoon; Zisman, Amnon; Graeber, Thomas G.; Eisenberg, David P.; McBride, William H.; Nguyen, David; Tso, Cho-Lea; Belldegrun, Arie S.

doi:10.1002/pros.10226

Cited by 20 publications

(17 citation statements)

References 15 publications

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“…During any of these steps, tumor cells interact with host factors in the microenvironment and will therefore will be subject to selection [57]. That there is actually a potential, selectable cellular heterogeneity also within PCa cell lines was shown by establishing LNCaP subclones displaying different tumor incidence or metastatic potential [58][59][60][61].…”

Section: Discussionmentioning

confidence: 99%

Anti-metastatic effects of liposomal gemcitabine in a human orthotopic LNCaP prostate cancer xenograft model

Jantscheff

Ziroli²,

Esser³

et al. 2009

Clin Exp Metastasis

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Fatal outcomes of prostate carcinoma (PCa) mostly result from metastatic spread rather than from primary tumor burden. Here, we monitored growth and metastatic spread of an orthotopic luciferase/GFP-expressing LNCaP PCa xenograft model in SCID mice by in vivo imaging and in vitro luciferase assay of tissues homogenates. Although the metastatic spread generally shows a significant correlation to primary tumor volumes, the susceptibility of various tissues to metastatic invasion was different in the number of affected animals as well as in absolute metastatic burden in the individual tissues. Using this xenograft model we showed that treatment with liposomal gemcitabine (GemLip) inhibited growth of the primary tumors (83.9 +/- 6.4%; P = 0.009) as well as metastatic burden in lymph nodes (95.6 +/- 24.0%; P = 0.047), lung (86.5 +/- 10.5%; P = 0.015), kidney (88.4 +/- 9.2%; P = 0.045) and stomach (79.5 +/- 6.6%; P = 0.036) already at very low efficient concentrations (8 mg/kg) as compared to conventional gemcitabine (360 mg/kg). Our data show that this orthotopic LNCaP xenograft PCa model seems to reflect the clinical situation characterized by the fact that at time of diagnosis, prostate neoplasms are biologically heterogeneous and thus, it is a useful model to investigate new anti-metastatic therapies.

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Section: Discussionmentioning

confidence: 99%

Anti-metastatic effects of liposomal gemcitabine in a human orthotopic LNCaP prostate cancer xenograft model

Jantscheff

Ziroli²,

Esser³

et al. 2009

Clin Exp Metastasis

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“…RNA preparations from similar, but non-identical, biopsy samples can yield dissimilar results [35], and RNA from different versions of the same cell line can yield widely different expression profiles [36,37]. …”

Section: Discussionmentioning

confidence: 99%

Three microarray platforms: an analysis of their concordance in profiling gene expression

et al. 2005

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Background: Microarrays for the analysis of gene expression are of three different types: short oligonucleotide (25-30 base), long oligonucleotide (50-80 base), and cDNA (highly variable in length). The short oligonucleotide and cDNA arrays have been the mainstay of expression analysis to date, but long oligonucleotide platforms are gaining in popularity and will probably replace cDNA arrays. As part of a validation study for the long oligonucleotide arrays, we compared and contrasted expression profiles from the three formats, testing RNA from six different cell lines against a universal reference standard.

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“…This relationship may explain the strikingly tight relationship between AR expression and expression of wild-type p53 in vitro revealed by a survey of the literature (Table 1). Most recently, in new androgen-independent prostate cancer cell lines derived from LNCaP via in vitro deprivation (Patel et al, 2000), low levels of p53 were reported along with almost undetectable levels of PSA mRNA and reduced levels of AR mRNA (Freedland et al, 2003). Similarly, in breast cancer a consistent relationship appears to exist between the expression of estrogen receptor (ER) and wild-type p53 expression (Caleffi et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of p53 function diminishes androgen receptor-mediated signaling in prostate cancer cell lines

et al. 2004

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Current therapy for advanced prostate cancer is mainly based on androgen deprivation, although most patients relapse to androgen-insensitive disease. Several mechanisms contributing to androgen-independent growth including alterations in the structure or expression of the androgen receptor (AR) and its cofactors have been identified. Recent evidence suggests that p53 is involved in androgen signaling. The analysis of the effect of p53 on androgen signaling was performed in 22Rv1 and LNCaP prostate cancer cells that express both p53 and AR. The overexpression of p53 diminished the androgenic response in both cell lines in a reporter gene assay. Conversely, the inhibition of p53 by three different p53 inhibitors, Pifithrin-1a (PFT-1a), an inhibitor of p53-dependent transactivation; MDM2, a regulator of p53 expression; and a dominant-negative N-terminally truncated p53 gene also reduced transactivation of androgen-dependent reporter genes. The inactivation of p53 by PFT-1a decreased AR-protein expression in both 22Rv1 and LNCaP cells. Our findings confirm that the overexpression of wild-type p53 decreases androgen function, whereas p53 expression at physiological levels stabilizes AR signaling. Thus, our findings suggest that there is a balance of AR and p53 expression during the androgendependent growth of prostate cancer, which is obliterated during further progression of the disease.

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Heterogeneity of molecular targets on clonal cancer lines derived from a novel hormone‐refractory prostate cancer tumor system

Cited by 20 publications

References 15 publications

Anti-metastatic effects of liposomal gemcitabine in a human orthotopic LNCaP prostate cancer xenograft model

Anti-metastatic effects of liposomal gemcitabine in a human orthotopic LNCaP prostate cancer xenograft model

Three microarray platforms: an analysis of their concordance in profiling gene expression

Inhibition of p53 function diminishes androgen receptor-mediated signaling in prostate cancer cell lines

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