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Zelivianski, Stanislav; Dean, Jeanenne; Madhavan, Deepak; Lin, Fen Fen; Lin, Ming‐Fong

doi:10.1023/a:1007010304194

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…In NE subclone cells, in addition to the increased level of NSE expression, we found that the protein level of RPTPa is elevated. Our previous data showed that RPTPa mRNA (Zelivianski et al, 2000) and protein (Zelivianski et al, 2001) levels are increased in LNCaP cells after short-term steroid withdrawal without known biological implications. Transient transfection clearly demonstrates that overexpression of the wild-type RPTPa results in activation of ERK (Figures 6a, c, 7a) as well as elevation of NSE level in a dose-dependent fashion (Figures 6a, c, 7a).…”

Section: Discussionmentioning

confidence: 99%

“…Since RPTPa plays an important role in neuronal differentiation (den Hertog et al, 1993;van Inzen et al, 1996), and has low level of expression in C-33 LNCaP cells (Zelivianski et al, 2000), the expression of RPTPa in the established NE subclone cells was analysed. As shown in Figure 3a, the protein level of RPTPa in both NE subclone cells was elevated by over fivefold, higher than that in C-33 LNCaP cells.…”

Section: Expression Of Rptpa In Ne Subclone Cellsmentioning

confidence: 99%

“…Thus, RPTPa plays a critical role in numerous differentiation activities in different cell types. Although RPTPa is expressed in normal prostate cells and prostate cancer cells (Zelivianski et al, 2000(Zelivianski et al, , 2001, the functional role of RPTPa in human prostate cells remains to be studied.…”

Section: Introductionmentioning

confidence: 99%

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Receptor protein tyrosine phosphatase alpha signaling is involved in androgen depletion-induced neuroendocrine differentiation of androgen-sensitive LNCaP human prostate cancer cells

et al. 2003

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The neuroendocrine (NE) cells represent the third cell population in the normal prostate. Results of several clinical studies strongly indicate that the NE cell population is greatly increased in prostate carcinomas during androgen ablation therapy that correlates with hormone-refractory growth and poor prognosis. However, the mechanism of NE cell enrichment in prostate carcinoma remains an enigma. We investigated the molecular mechanism by which androgen-sensitive C-33 LNCaP human prostate cancer cells become NE-like cells in an androgen-reduced environment, mimicking clinical phenomenon. In the androgen-depleted condition, androgen-sensitive C-33 LNCaP cells gradually acquired the NE-like morphology and expressed an increased level of neuron-specific enolase (NSE), a classical marker of neuronal cells. Several NE-like subclone cells were established. Biochemical characterizations of these subclone cells showed that receptor-type protein-tyrosine phosphatase alpha (RPTPalpha) is elevated and ERK is constitutively activated, several folds higher than that in parental cells. In androgen-depleted condition, PD98059, an MEK inhibitor, could efficiently block not only the activation of ERK, but also the acquisition of the NE-like morphology and the elevation of NSE in C-33 LNCaP cells. In RPTPalpha cDNA-transfected C-33 LNCaP cells, ERK was activated and NSE was elevated. In those cells in the presence of PD98059, the ERK activation and NSE elevation were abolished, following a dose-response fashion. Additionally, in constitutively active MEK mutant cDNA-transfected C-33 LNCaP cells, ERK was activated and NSE level was elevated, and cells obtained the NE-like phenotype. Our data collectively indicated that RPTPalpha signaling via ERK is involved in the NE transdifferentiation of androgen-sensitive C-33 LNCaP human prostate cancer cells in the androgen-depleted condition.

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Section: Discussionmentioning

confidence: 99%

Section: Expression Of Rptpa In Ne Subclone Cellsmentioning

confidence: 99%

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Receptor protein tyrosine phosphatase alpha signaling is involved in androgen depletion-induced neuroendocrine differentiation of androgen-sensitive LNCaP human prostate cancer cells

et al. 2003

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The role of protein tyrosine phosphatases in prostate cancer biology

Nunes‐Xavier

Mingo

López

et al. 2019

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Multipathways for transdifferentiation of human prostate cancer cells into neuroendocrine-like phenotype

Zelivianski

Verni²,

Moore

et al. 2001

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The neuroendocrine (NE) cell is a minor cell population in normal human prostate glands. The number of NE cells is increased in advanced hormone-refractory prostate carcinomas (PCA). The mechanism of increased NE cell population in these advanced tumors is poorly understood. We examined molecular mechanisms which may be involved in the regulation of the transdifferentiation process of human PCA cells leading to a NE phenotype. We compared PCA cell lines LNCaP and PC-3 in the following medium conditions: steroid-reduced (SR), interleukin-6 (IL-6)-supplemented, or dibutyrate cAMP (db-cAMP)-supplemented. We found that androgen-responsive C-33 LNCaP cells responded to all treatments, having a neuronal-like morphology. In contrast, C-81 LNCaP cells, having a decreased androgen responsiveness, had a less pronounced effect although followed a similar trend. Androgen-unresponsive PC-3 cells showed little change in their morphology. Grown in the SR condition, the level of neuron-specific enolase (NSE), a marker of neuronal cells, was upregulated in C-33 LNCaP cells, while to a lesser degree in the presence of IL-6. In the presence of db-cAMP, the NSE level in C-33 cells was decreased, lower than that in control cells. An opposite effect was observed for C-81 LNCaP cells. Nevertheless, the NSE level was only elevated in db-cAMP-treated PC-3 cells, but no change was found in PC-3 cells grown in the SR- or IL-6-supplemented medium. Thus, a similar gross phenotypic change may correlate with differential molecular expressions. We also analyzed the expression of protein tyrosine phosphatase alpha (RPTPalpha) since it plays a critical role in normal neuronal differentiation and signaling. Our results showed that the expression of RPTPalpha correlates with the NE phenotypic change of LNCaP cells in the SR condition. In summary, our data clearly show that the molecular process by which cultured human prostate cancer cells undergo a transdifferentiation process to a NE cell-like phenotype is accompanied by differential expressions of different markers, and a gross NE cell-like phenotype can occur by exposing PCA cells to different pharmacological agents.

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Cited by 5 publications

References 38 publications

Receptor protein tyrosine phosphatase alpha signaling is involved in androgen depletion-induced neuroendocrine differentiation of androgen-sensitive LNCaP human prostate cancer cells

Receptor protein tyrosine phosphatase alpha signaling is involved in androgen depletion-induced neuroendocrine differentiation of androgen-sensitive LNCaP human prostate cancer cells

The role of protein tyrosine phosphatases in prostate cancer biology

Multipathways for transdifferentiation of human prostate cancer cells into neuroendocrine-like phenotype

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