Neuroendocrine Expression in Node Positive Prostate Cancer: Correlation With Systemic Progression and Patient Survival

Bostwick, David G.; Qian, Junqi; Pacelli, Anna; Zincke, Horst; Blute, Michael L.; Bergstralh, Erik J.; Slezak, Jeffrey M.; Liu, Cheng

doi:10.1016/s0022-5347(05)64626-5

Cited by 83 publications

(58 citation statements)

References 25 publications

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“…CaP progression is associated with significant changes in neuronal/NE differentiation of prostatic epithelial cells 25,26 and 'neuronal' genes/markers, including SCN9A/Nav1.7, are both upregulated in CaP and have potential functional roles in metastasis. 29,[31][32][33] In this study, we observed Brn3a[s]-specific transcriptional regulation of SCN9A/Nav1.7 in PC-3 cells with both stable and transient overexpression of this transcription factor.…”

Section: Upregulation Of Brn-3a[s] In Cap and Role In Growthmentioning

confidence: 99%

“…25,26 In particular, pore-forming a-subunits (but not auxillary b-subunits) of voltage-gated Na þ channels (VGSCs), which are classically expressed at high levels in neuronal/excitable tissues, are overexpressed in CaP in vitro 27,28 and in vivo. 29,30 Importantly, expressed neuronal/NE markers are likely to play a direct role in disease progression.…”

Section: Introductionmentioning

confidence: 99%

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Brn-3a neuronal transcription factor functional expression in human prostate cancer

Diss

Faulkes

Walker

et al. 2005

Prostate Cancer Prostatic Dis

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Neuroendocrine differentiation has been associated with prostate cancer (CaP). Brn-3a (short isoform) and Brn-3c, transcriptional controllers of neuronal differentiation, were readily detectable in human CaP both in vitro and in vivo. Brn-3a expression, but not Brn-3c, was significantly upregulated in 450% of tumours. Furthermore, overexpression of this transcription factor in vitro (i) potentiated CaP cell growth and (ii) regulated the expression of a neuronal gene, the Nav1.7 sodium channel, concomitantly upregulated in human CaP, in an isoform-specific manner. It is concluded that targeting Brn-3a could be a useful strategy for controlling the expression of multiple genes that promote CaP.

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Section: Upregulation Of Brn-3a[s] In Cap and Role In Growthmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Brn-3a neuronal transcription factor functional expression in human prostate cancer

Diss

Faulkes

Walker

et al. 2005

Prostate Cancer Prostatic Dis

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“…Their studies, however, included patients with different stages of the disease, unlike our study on patients with prostate cancer at a single stage. Aprikian et al (19) and Bostwick et al (16) studied advanced prostate cancer with lymph node metastasis, and reported no significant difference in survival rate for NE cell differentiation. In their in vivo research using PC-310 human prostate cancer xenograft cells, Jongsma et al (20) reported that androgen-dependent tumors decreased by apoptosis within a few days following castration, with 50% of the surviving cancer cells being positive for Cg A.…”

Section: Discussionmentioning

confidence: 99%

“…Bostwick et al (16) used the number of positive cells as the criterion of positive staining. As Cg A-positive cells are observed in small numbers in normal prostate epithelium, however, in this study we defined Cg A-positive as the presence of positive cells in more than 10% of the surface area of the tumor (7).…”

Section: Discussionmentioning

confidence: 99%

Is neuroendocrine cell differentiation detected using chromogranin A from patients with bone metastatic prostate cancer a prognostic factor for outcome?

Yamada

Nakamura²,

Aoki³

et al. 2006

Oncol Rep

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Abstract.We evaluated the usefulness of overexpression of neuroendrocrine (NE) cell differentiation determined by immunohistochemical staining for chromogranin A (Cg A) in diagnostic needle biopsy specimens of bone metastatic prostate cancers. A total of 50 patients diagnosed as having bone metastatic prostate cancer were studied. The period of observation was between 6.9 and 79.4 months (median 48.7 months). Cg A was detected by immunostaining using the labeled streptavidin biotin method. Cg A-positivity was defined as the presence of immunostained cells in 10% or more of the tumor. All statistical analyses were carried out using the Statistical Package for Social Sciences Software, version 10.0 for Windows. Eleven patients (22%) were classified into the Cg A-positive group. There were no significant differences in clinical data between the Cg Apositive and Cg A-negative groups. The 5-year causespecific survival rate was 34.1% for the Cg A-positive group and 55.2% for the Cg A-negative group (p=0.3763). The 3-year non-recurrence rate was 9.1% for the Cg A-positive group and 35.9% for the Cg A-negative group, and this difference was significant (p=0.0253). The 3-year causespecific survival rates after recurrence were 38.4% and 42.3% respectively (p=0.8125). We consider that NE cell differentiation of the primary tumor in cases of bone metastatic prostate cancer is not a prognostic factor for outcome.

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“…There is debate in the field as to whether neuroendocrine cells are most important for early prostate cancer development, progression to a hormone-refractory state, metastasis, or a combination of all three (2,42,44,45). Although many reports indicate a positive correlation between the presence of a neuroendocrine population and prostate cancer, the degree of neuroendocrine positive staining does not always correlate with tumor grade (19,42,44).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of prostate cancer therapeutics on neuroendocrine transdifferentiation

Frigo

McDonnell

2008

Molecular Cancer Therapeutics

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Androgen ablation therapy is widely used for the treatment of advanced prostate cancer. However, the effectiveness of this intervention strategy is generally short-lived as the disease ultimately progresses to a hormone-refractory state. In recent years, it has become clear that even in antiandrogen-resistant cancers the androgen receptor (AR) signaling axis is intact and is required for prostate cancer growth. Thus, there is a heightened interest in developing small molecules that function in part by downregulating AR expression in tumors. Paradoxically, AR expression has been shown to be important in preventing the transdifferentiation of epithelial prostate cancer cells toward a neuroendocrine phenotype associated with tumor progression. Consequently, we have evaluated the relative effect of prostate cancer therapeutics that function in part by depleting AR levels on neuroendocrine differentiation in established cellular models of prostate cancer. These studies reveal that although histone deacetylase inhibitors can down-regulate AR expression they increase the expression of neuroendocrine markers and alter cellular morphology. Inhibition of AR signaling using classic AR antagonists or small interfering RNA -mediated AR ablation induces incomplete neuroendocrine differentiation. Importantly, the Hsp90 inhibitor geldanamycin effectively down-regulates AR expression while having no effect on neuroendocrine differentiation. Taken together, these data show that the phenotypic responses to pharmacologic agents used in the clinic to prevent the progression of prostate cancer are not equivalent, a finding of significant therapeutic importance. [Mol Cancer Ther 2008;7(3):659 -69]

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Neuroendocrine Expression in Node Positive Prostate Cancer: Correlation With Systemic Progression and Patient Survival

Cited by 83 publications

References 25 publications

Brn-3a neuronal transcription factor functional expression in human prostate cancer

Brn-3a neuronal transcription factor functional expression in human prostate cancer

Is neuroendocrine cell differentiation detected using chromogranin A from patients with bone metastatic prostate cancer a prognostic factor for outcome?

Differential effects of prostate cancer therapeutics on neuroendocrine transdifferentiation

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