Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process

BACKGROUND: Prostate cancer is characterized by heterogeneity in the clinical course that often does not correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. METHODS: Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. RESULTS: The metastatic samples are highly heterogenous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodelling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). CONCLUSION: We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer

Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption

To prevent dehydration, terrestrial animals and humans have developed a sensitive and versatile system to maintain their water homeostasis. In states of hypernatremia or hypovolemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary and binds its type-2 receptor in renal principal cells. This triggers an intracellular cAMP signaling cascade, which phosphorylates aquaporin-2 (AQP2) and targets the channel to the apical plasma membrane. Driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels. When water homeostasis is restored, AVP levels decline, and AQP2 is internalized from the plasma membrane, leaving the plasma membrane watertight again. The action of AVP is counterbalanced by several hormones like prostaglandin E2, bradykinin, dopamine, endothelin-1, acetylcholine, epidermal growth factor, and purines. Moreover, AQP2 is strongly involved in the pathophysiology of disorders characterized by renal concentrating defects, as well as conditions associated with severe water retention. This review focuses on our recent increase in understanding of the molecular mechanisms underlying AVP-regulated renal water transport in both health and disease

Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process

Abstract Background Prostate cancer is characterized by heterogeneity in the clinical course that often does not correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. Methods Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. Results The metastatic samples are highly heterogenous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodelling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). Conclusion We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer.</p

Gene Expression Profiles of Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Rationale: The molecular mechanisms underlying acute exacerbations of idiopathic pulmonary fibrosis (IPF) are poorly understood. We studied the global gene expression signature of acute exacerbations of IPF

Box plots of gene expression values for selected genes in donor prostate samples, primary prostate cancer and metastatic prostate samples

<p><b>Copyright information:</b></p><p>Taken from "Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process"</p><p>http://www.biomedcentral.com/1471-2407/7/64</p><p>BMC Cancer 2007;7():64-64.</p><p>Published online 12 Apr 2007</p><p>PMCID:PMC1865555.</p><p></p

Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process-1

<p><b>Copyright information:</b></p><p>Taken from "Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process"</p><p>http://www.biomedcentral.com/1471-2407/7/64</p><p>BMC Cancer 2007;7():64-64.</p><p>Published online 12 Apr 2007</p><p>PMCID:PMC1865555.</p><p></p>lor coded boxes represents metastatic or primary samples; the bottom row represents the organ from which the sample was obtained

Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process-2

<p><b>Copyright information:</b></p><p>Taken from "Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process"</p><p>http://www.biomedcentral.com/1471-2407/7/64</p><p>BMC Cancer 2007;7():64-64.</p><p>Published online 12 Apr 2007</p><p>PMCID:PMC1865555.</p><p></p>ifferentially expression genes is shown