.JPG?ad=18503&adview=true)
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
Cancer Center and Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908
Neuroendocrine (NE) cells occur as scattered foci within prostatic adenocarcinoma, similar to their distribution within ductal epithelial cells of the normal prostate. However, the density of NE cells is often greater in prostate carcinomas than in normal tissue, and the frequency of NE cells correlates with tumor grade, loss of androgen sensitivity, autocrine/paracrine activity, and poor prognosis. Although NE cells are nonmitotic, proliferating cells are found in direct proximity to them, suggesting that NE cells provide paracrine stimuli for surrounding carcinoma cells. In vitro, differentiation of the LNCaP and PC3M prostatic tumor cell lines to a NE phenotype can be induced by dibutyryl cyclic AMP (cAMP), suggesting that physiological agents that increase intracellular concentrations of cAMP might regulate NE differentiation in vivo. Indeed, we demonstrate in this report that LNCaP cells acquire NE characteristics in response to treatment with physiological and pharmacological agents that elevate intracellular cAMP, agents such as epinephrine, isoproterenol, forskolin, and dibutyryl cAMP. The androgen-independent LNCaP-derived cell line C4-2 also responded to these agents, indicating that cells representing later stages of tumor progression are also capable of differentiation. The NE phenotype in this study was monitored by the appearance of dense core granules in the cytoplasm, the extension of neuron-like processes, loss of mitogenic activity, and expression of the NE markers neuron-specific enolase, parathyroid hormone-related peptide, neurotensin, serotonin, and chromogranin A. However, contrary to previous reports, we observed rapid loss of the NE phenotype in both LNCaP and C4-2 cells upon withdrawal of inducing agents. Withdrawal also resulted in a rapid, dramatic increase in tyrosine kinase and mitogen-activated protein kinase activities, suggesting that activation of these intracellular signaling enzymes may be important for reentry into the cell cycle. Together, these results indicate that chronic cAMP-mediated signaling is required to block proliferation of prostate tumor cells and to induce NE differentiation.
This article has been cited by other articles:
|
|
 |
|
  F. Gackiere, G. Bidaux, P. Delcourt, F. Van Coppenolle, M. Katsogiannou, E. Dewailly, A. Bavencoffe, M. T. Van Chuoi-Mariot, B. Mauroy, N. Prevarskaya, et al. CaV3.2 T-type Calcium Channels Are Involved in Calcium-dependent Secretion of Neuroendocrine Prostate Cancer Cells J. Biol. Chem., April 11, 2008; 283(15): 10162 - 10173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Frigo and D. P. McDonnell Differential effects of prostate cancer therapeutics on neuroendocrine transdifferentiation Mol. Cancer Ther., March 1, 2008; 7(3): 659 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-C. Yuan, S. Veeramani, and M.-F. Lin Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells Endocr. Relat. Cancer, September 1, 2007; 14(3): 531 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gong, J. Lee, H. Akio, P. N. Schlegel, and R. Shen Attenuation of Apoptosis by Chromogranin A-Induced Akt and Survivin Pathways in Prostate Cancer Cells Endocrinology, September 1, 2007; 148(9): 4489 - 4499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Valentini, M. Biancolella, F. Amati, P. Gravina, R. Miano, G. Chillemi, A. Farcomeni, S. Bueno, G. Vespasiani, A. Desideri, et al. Valproic Acid Induces Neuroendocrine Differentiation and UGT2B7 Up-Regulation in Human Prostate Carcinoma Cell Line Drug Metab. Dispos., June 1, 2007; 35(6): 968 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Deeble, M. E. Cox, H. F. Frierson Jr., R. A. Sikes, J. B. Palmer, R. J. Davidson, E. V. Casarez, G. P. Amorino, and S. J. Parsons Androgen-Independent Growth and Tumorigenesis of Prostate Cancer Cells Are Enhanced by the Presence of PKA-Differentiated Neuroendocrine Cells Cancer Res., April 15, 2007; 67(8): 3663 - 3672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wu and J. Huang Phosphatidylinositol 3-Kinase-AKT-Mammalian Target of Rapamycin Pathway Is Essential for Neuroendocrine Differentiation of Prostate Cancer J. Biol. Chem., February 9, 2007; 282(6): 3571 - 3583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Desai, A.-H. Ma, C. G. Tepper, H.-W. Chen, and H.-J. Kung Inappropriate Activation of the Androgen Receptor by Nonsteroids: Involvement of the Src Kinase Pathway and Its Therapeutic Implications Cancer Res., November 1, 2006; 66(21): 10449 - 10459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Thomas, S. Chigurupati, M. Anbalagan, and G. Shah Calcitonin Increases Tumorigenicity of Prostate Cancer Cells: Evidence for the Role of Protein Kinase A and Urokinase-Type Plasminogen Receptor Mol. Endocrinol., August 1, 2006; 20(8): 1894 - 1911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-C. Yuan, S. Veeramani, F.-F. Lin, D. Kondrikou, S. Zelivianski, T. Igawa, D. Karan, S. K. Batra, and M.-F. Lin Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells. Endocr. Relat. Cancer, March 1, 2006; 13(1): 151 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chen, Y. Wang, H. Yu, F. Wang, and W. Xu The Cross Talk Between Protein Kinase A- and RhoA-Mediated Signaling in Cancer Cells Experimental Biology and Medicine, November 1, 2005; 230(10): 731 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Krueckl, R. A. Sikes, N. M. Edlund, R. H. Bell, A. Hurtado-Coll, L. Fazli, M. E. Gleave, and M. E. Cox Increased Insulin-Like Growth Factor I Receptor Expression and Signaling Are Components of Androgen-Independent Progression in a Lineage-Derived Prostate Cancer Progression Model Cancer Res., December 1, 2004; 64(23): 8620 - 8629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hu, T. Wang, G. D. Stormo, and J. I. Gordon RNA interference of achaete-scute homolog 1 in mouse prostate neuroendocrine cells reveals its gene targets and DNA binding sites PNAS, April 13, 2004; 101(15): 5559 - 5564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kim, R. M. Adam, K. R. Solomon, and M. R. Freeman Involvement of Cholesterol-Rich Lipid Rafts in Interleukin-6-Induced Neuroendocrine Differentiation of LNCaP Prostate Cancer Cells Endocrinology, February 1, 2004; 145(2): 613 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Brody, S. S. Kadkol, M. C. Hauer, F. Rajaii, J. Lee, and G. R. Pasternack pp32 Reduction Induces Differentiation of TSU-Pr1 Cells Am. J. Pathol., January 1, 2004; 164(1): 273 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Farini, A. Puglianiello, C. Mammi, G. Siracusa, and C. Moretti Dual Effect of Pituitary Adenylate Cyclase Activating Polypeptide on Prostate Tumor LNCaP Cells: Short- and Long-Term Exposure Affect Proliferation and Neuroendocrine Differentiation Endocrinology, April 1, 2003; 144(4): 1631 - 1643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Mariot, K. Vanoverberghe, N. Lalevee, M. F. Rossier, and N. Prevarskaya Overexpression of an alpha 1H (Cav3.2) T-type Calcium Channel during Neuroendocrine Differentiation of Human Prostate Cancer Cells J. Biol. Chem., March 22, 2002; 277(13): 10824 - 10833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kim, R. M. Adam, and M. R. Freeman Activation of the Erk Mitogen-activated Protein Kinase Pathway Stimulates Neuroendocrine Differentiation in LNCaP Cells Independently of Cell Cycle Withdrawal and STAT3 Phosphorylation Cancer Res., March 1, 2002; 62(5): 1549 - 1554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-F. Lee, J. Guan, Y. Qiu, and H.-J. Kung Neuropeptide-Induced Androgen Independence in Prostate Cancer Cells: Roles of Nonreceptor Tyrosine Kinases Etk/Bmx, Src, and Focal Adhesion Kinase Mol. Cell. Biol., December 15, 2001; 21(24): 8385 - 8397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Deeble, D. J. Murphy, S. J. Parsons, and M. E. Cox Interleukin-6- and Cyclic AMP-Mediated Signaling Potentiates Neuroendocrine Differentiation of LNCaP Prostate Tumor Cells Mol. Cell. Biol., December 15, 2001; 21(24): 8471 - 8482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Murillo, H. Huang, L. J. Schmidt, D. I. Smith, and D. J. Tindall Role of PI3K Signaling in Survival and Progression of LNCaP Prostate Cancer Cells to the Androgen Refractory State Endocrinology, November 1, 2001; 142(11): 4795 - 4805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Wilson, Y. Oh, V. Hwa, and R. G. Rosenfeld Interaction of IGF-Binding Protein-Related Protein 1 with a Novel Protein, Neuroendocrine Differentiation Factor, Results in Neuroendocrine Differentiation of Prostate Cancer Cells J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4504 - 4511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Yehia, R. Razavi, E. Memin, F. Schlotter, and C. A. Molina The Expression of Inducible cAMP Early Repressor (ICER) Is Altered in Prostate Cancer Cells and Reverses the Transformed Phenotype of the LNCaP Prostate Tumor Cell Line Cancer Res., August 1, 2001; 61(16): 6055 - 6059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Agarwal, Y. Sharma, J. Zhao, and R. Agarwal A Polyphenolic Fraction from Grape Seeds Causes Irreversible Growth Inhibition of Breast Carcinoma MDA-MB468 Cells by Inhibiting Mitogen-activated Protein Kinases Activation and Inducing G1 Arrest and Differentiation Clin. Cancer Res., July 1, 2000; 6(7): 2921 - 2930. [Abstract] [Full Text]
|
|
|
|
|
|
M. E. Cox, P. D. Deeble, E. A. Bissonette, and S. J. Parsons Activated 3',5'-Cyclic AMP-dependent Protein Kinase Is Sufficient to Induce Neuroendocrine-like Differentiation of the LNCaP Prostate Tumor Cell Line J. Biol. Chem., April 28, 2000; 275(18): 13812 - 13818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yuasa, J. Kotera, K. Fujishige, H. Michibata, T. Sasaki, and K. Omori Isolation and Characterization of Two Novel Phosphodiesterase PDE11A Variants Showing Unique Structure and Tissue-specific Expression J. Biol. Chem., September 29, 2000; 275(40): 31469 - 31479. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
