Expression of CRABP1, GRP, and RERG mRNA in clinically non-functioning and functioning pituitary adenomas

Background: Pituitary tumors account for approximately 10–15% of intracranial neoplasms. Aim: Using the cDNA microarray method, we have previously compared expression under two distinct conditions: a pool of 4 clinically non-functioning pituitary adenomas (NFPA) and a spinal cord metastasis of a non-functioning pituitary carcinoma, in order to gain biological insights into genomic changes of pituitary neoplasias. In the present study, we further investigated the mRNA expression of 3 selected genes previously described as being involved in other neoplasias based on a series of 60 pituitary adenomas: CRABP1 (cellular retinoic acid binding protein 1), GRP (gastrin-releasing peptide), and RERG (Ras-related, estrogen-regulated, growth inhibitor). Material and methods: The expression of CRABP1, GRP, and RERG was determined by quantitative RT-PCR. Results: A significantly higher content of CRABP1 mRNA was observed in NFPA compared to functioning adenomas, and PRL-secreting adenomas showed a lower expression of this gene compared to normal pituitary. A lower expression of GRP mRNA was detected in NFPA compared to normal pituitary and also to functioning adenomas. RERG mRNA was overexpressed in NFPA in comparison to functioning adenomas and to normal pituitary. Among the functioning adenomas, only the ACTH-secreting adenomas presented a higher expression of RERG mRNA compared to normal pituitary. Conclusions: The findings of differential expression of CRABP1 in prolactinomas and of RERG in NFPA compared to normal pituitary suggests that retinoic acid and estrogen receptor, respectively, could be involved in the tumorigenesis of these adenomas subtypes. Additional studies are required to further confirm this hypothesis.

[1]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[2]  S. Schulz,et al.  Immunohistochemical detection of bombesin receptor subtypes GRP-R and BRS-3 in human tumors using novel antipeptide antibodies , 2006, Virchows Archiv.

[3]  S Rozen,et al.  Primer3 on the WWW for general users and for biologist programmers. , 2000, Methods in molecular biology.

[4]  C. Denef,et al.  Evidence for the presence of gastrin-releasing peptide immunoreactivity in rat anterior pituitary corticotrophs and lactotrophs, AtT20 cells, and GH3 cells: failure to demonstrate participation in local control of hormone release. , 1991, Endocrinology.

[5]  A. de la Chapelle,et al.  Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma , 2003, International journal of cancer.

[6]  U. Knigge,et al.  Gastrin-releasing peptide stimulation of corticotropin secretion in male rats. , 1992, Endocrinology.

[7]  G. Stalla,et al.  Potential of retinoic acid derivatives for the treatment of corticotroph pituitary adenomas , 2009, Reviews in Endocrine and Metabolic Disorders.

[8]  L. Gudas,et al.  The level of CRABP-I expression influences the amounts and types of all-trans-retinoic acid metabolites in F9 teratocarcinoma stem cells. , 1992, The Journal of biological chemistry.

[9]  D. Chung,et al.  Gastrin-releasing peptide receptor silencing suppresses the tumorigenesis and metastatic potential of neuroblastoma , 2008, Proceedings of the National Academy of Sciences.

[10]  C. Denef,et al.  Expression of the genes encoding bombesin-related peptides and their receptors in anterior pituitary tissue , 1993, Molecular and Cellular Endocrinology.

[11]  J. Mulshine,et al.  Antitumor activity of a monoclonal antibody directed against gastrin-releasing peptide in patients with small cell lung cancer. , 1997, Chest.

[12]  P. Beck‐Peccoz,et al.  Effect of 9-cis Retinoic Acid on Dopamine D2 Receptor Expression in Pituitary Adenoma Cells , 2008, Experimental biology and medicine.

[13]  L. Gudas,et al.  Overexpression of the cellular retinoic acid binding protein-I (CRABP- I) results in a reduction in differentiation-specific gene expression in F9 teratocarcinoma cells , 1991, The Journal of cell biology.

[14]  R. Jensen,et al.  Mammalian Bombesin Receptors : Nomenclature , Distribution , Pharmacology , Signaling , and Functions in Normal and Disease States , 2008 .

[15]  M. Donovan,et al.  The cellular retinoic acid binding proteins , 1995, The Journal of Steroid Biochemistry and Molecular Biology.

[16]  B. Swearingen,et al.  Differential Expression of Estrogen Receptor-β (ERβ) in Human Pituitary Tumors: Functional Interactions with ERα and a Tumor-Specific Splice Variant1 , 1998 .

[17]  E. Uhl,et al.  Retinoic acid prevents experimental Cushing syndrome. , 2001, The Journal of clinical investigation.

[18]  G. Norstedt,et al.  Identification of genes with higher expression in human uterine leiomyomas than in the corresponding myometrium. , 2002, Molecular human reproduction.

[19]  Y. Byun,et al.  The effect of cellular retinoic acid binding protein-I expression on the CYP26-mediated catabolism of all-trans retinoic acid and cell proliferation in head and neck squamous cell carcinoma. , 2004, Metabolism: clinical and experimental.

[20]  D. Chung,et al.  Gastrin-Releasing Peptide Is a Growth Factor for Human Neuroblastomas , 2002, Annals of surgery.

[21]  J. Inazawa,et al.  Frequent methylation-associated silencing of a candidate tumor-suppressor, CRABP1, in esophageal squamous-cell carcinoma , 2007, Oncogene.

[22]  M. Loda,et al.  CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies , 2006, Gut.

[23]  David Botstein,et al.  RERG Is a Novel ras-related, Estrogen-regulated and Growth-inhibitory Gene in Breast Cancer* , 2001, The Journal of Biological Chemistry.

[24]  S. Wiseman,et al.  TIMP1 and SERPIN‐A overexpression and TFF3 and CRABP1 underexpression as biomarkers for papillary thyroid carcinoma , 2004, Head & neck.

[25]  P. Viganò,et al.  Accumulation of retinoid X receptor-alpha in uterine leiomyomas is associated with a delayed ligand-dependent proteasome-mediated degradation and an alteration of its transcriptional activity. , 2007, Molecular endocrinology.

[26]  Xianquan Zhan,et al.  Novel molecular signaling and classification of human clinically nonfunctional pituitary adenomas identified by gene expression profiling and proteomic analyses. , 2005, Cancer research.

[27]  J. Burdman,et al.  Estrogen Receptors in Human Pituitary Tumors , 2008, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[28]  Darrell R. Abernethy,et al.  International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels , 2003, Pharmacological Reviews.

[29]  J. Herman,et al.  CpG island methylator phenotype in colorectal cancer. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[30]  K. Szepesházi,et al.  Targeted cytotoxic analogue of bombesin/ gastrin-releasing peptide inhibits the growth of H-69 human small-cell lung carcinoma in nude mice , 1999, British Journal of Cancer.

[31]  D. Giannella‐Neto,et al.  Metallothionein Isoform 3 Gene Is Differentially Expressed in Corticotropin-Producing Pituitary Adenomas , 2006, Neuroendocrinology.

[32]  R. Ward,et al.  Colorectal cancer: a model for epigenetic tumorigenesis , 2006, Gut.

[33]  Xuanchun Wang,et al.  Gene expression profiling in human null cell pituitary adenoma tissue , 2007, Pituitary.

[34]  Z. Fang,et al.  Matrix metalloproteinase-9 is differentially expressed in nonfunctioning invasive and noninvasive pituitary adenomas and increases invasion in human pituitary adenoma cell line. , 2007, The American journal of pathology.

[35]  K. Horiguchi,et al.  Reduction of retinaldehyde dehydrogenase 1 expression and production in estrogen-induced prolactinoma of rat , 2008, Medical Molecular Morphology.

[36]  R. Lothe,et al.  ADAMTS1, CRABP1, and NR3C1 Identified as Epigenetically Deregulated Genes in Colorectal Tumorigenesis , 2006, Cellular oncology : the official journal of the International Society for Cellular Oncology.

[37]  Qinghua Wu,et al.  DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets , 2007, Molecular Cancer.

[38]  S. Czirják,et al.  Differential gene expression in pituitary adenomas by oligonucleotide array analysis. , 2005, European journal of endocrinology.

[39]  D. Brat,et al.  Novel patterns of gene expression in pituitary adenomas identified by complementary deoxyribonucleic acid microarrays and quantitative reverse transcription-polymerase chain reaction. , 2001, The Journal of clinical endocrinology and metabolism.

[40]  W. L. Dees,et al.  Evidence for a physiological role of hypothalamic gastrin-releasing peptide to suppress growth hormone and prolactin release in the rat. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[41]  R. Geffers,et al.  Cellular Retinoic Acid Binding Protein I: Expression and Functional Influence in Renal Cell Carcinoma , 2005, Tumor Biology.

[42]  Wook Kim,et al.  Expression of the RERG Gene is Gender-Dependent in Hepatocellular Carcinoma and Regulated by Histone Deacetyltransferases , 2006, Journal of Korean medical science.

[43]  S. Melmed,et al.  Diagnosis and management of nonfunctioning pituitary tumors. , 1996, Annual review of medicine.

[44]  F. Holsboer,et al.  Retinoic acid as a novel medical therapy for Cushing's disease in dogs. , 2006, Endocrinology.