Activation of the protein kinase A pathway in human endometrial stromal cells reveals sequential categorical gene regulation

作     者：Tierney, EP Tulac, S Huang, STJ Giudice, LC 

作者机构：Stanford Univ Sch Med Dept Gynecol & Obstet Div Reprod Endocrinol & Infertil Stanford CA 94305 USA 

出 版 物：《PHYSIOLOGICAL GENOMICS》 (生理基因组学)

年 卷 期：2003年第16卷第1期

页      面：47-66页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

基　　金：NICHD NIH HHS [U-01-HD-42298  R-01-HD-25220-12] Funding Source: Medline 

主　　题：endometrium decidualization implantation microarray technology 

摘      要：Decidualization of endometrial stromal cells is a prerequisite for human implantation and occurs in vivo in response to progesterone and involves activation of the protein kinase A ( PKA) pathway. The objective of this study was to determine the molecular signatures and patterns of gene expression during stimulation of this pathway with an analog of cAMP. Endometrial stromal cells from two subjects were treated with or without 8- Br- cAMP ( 1 mM) for 0, 2, 12, 24, 36, and 48 h and were processed for microarray analysis, screening for 12,686 genes and ESTs. Most abundantly upregulated genes included neuropeptides, immune genes, IGF family members, cell cycle regulators, extracellular matrix proteases, cholesterol trafficking, cell growth and differentiation, hormone signaling, and signal transduction. Most abundantly downregulated genes included activator of NF- kappa B, actin/ tropomyosin/ calmodulin binding protein, cyclin B, IGFBP- 5, alpha1 type XVI collagen, lipocortin III, L- kynurenine hydrolase, frizzle- related protein, and cyclin E2. RT- PCR validated upregulation of IGFBP- 1, preprosomatostatin, and IL- 11, and Northern analysis validated their kinetic upregulation. RT- PCR confirmed downregulation of IGFBP- 5, cyclin B, and TIL- 4. K- means analysis revealed four major patterns of up- and downregulated genes, and genes within each ontological group were categorized into these four kinetic patterns. Within each ontological group different patterns of temporal gene expression were observed, indicating that even genes within one functional category are regulated differently during activation of the PKA pathway in human endometrial stromal cells. Overall, the data demonstrate kinetic reprogramming of genes within specific functional groups and changes in genes associated with nucleic acid binding, cell proliferation, decreased G protein signaling, increased STAT pathway signaling, structural proteins, cellular differentiation, and secretory processes. These c