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Transcriptional control of the human cholecystokinin gene
225 GASTRIC ENDOCRINE CELL HYPERPLASIA IN CHRONIC ATROPHIC GASTRITIS Pasquinelli G, Santini D, Preda P, Salerno A, Bonora G. Cariani G. ~ r t i n e l l i G. Ist M~croscopia Elettronica, Anatomia patologica, Clinica bledica, Bologna University, 40128 Bologna , Italy. To further characterize the type of endocrine cells associated with chronic atrophic gastritis (CAG), a comparative inm~nohistochemical (IH), electron micro scopical (EM) and in~noelectronmicroscopical (IEM) study was carried out on m~Itiple ~cosal gastric biopsies including body, fundic and antral mucosa from ii patients with multifocal CAG. Hypergastrinemia was constantly documented in 3 cases and in 5 ~as undetermined. ~ increase of endocrine cells was found in all patients. Our results indicate a heterogeneous composition of the endocrine hyperplasia comprising G, ECn, ECL, D and DI cells. No substantial difference was found in the account of endocrine cells between body-fundic and antral muco sa. The G cell hyperplasia found within the fundic areas was always associated with metaplastic mucosa. An antral and non-antral hyperplasia of endocrine ceHs with highly dense undetermined granules (~ 100-380 nm) was constantly documented. Interestingly, inmalno-gold labelling fop gastrin was detected over the majPity of these latter granules while a few others contained somatostatin. It has been further inferred that the unreactive cells were of the ECL type. Our results indicate that an endocrine cells hyperplasia with heterogeneous cell comp_o sition may occur in multifocal CAG arising both in antral and non-antral mucosa. Although IH and EM are necessary for the identification of endocrine hyperplasias, IEM appear the mope effective, particularly, in discriminating the type of "undetermined" endocrine secretory granules.
TRANSCRIPTIONAL CONTROL OF T H E HUMAN CHOLECYSTOKININ GENE. Pedersen K, Nielsen FC, Rehfeld JF. Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Cholecystokinin (CCK) belongs to the gastrin/CCK family of regulatory peptides in the brain and gut. The CCK gene is expressed in a tissue specific and developmentally regulated manner, and the aim of the present study is to characterize the c/s and transacting elements which control transcription of the human CCK gene. The CCK promoter was cloned from human neuroblastoma SK-N-MC cells. A comparison of the rat and human sequences shows that the two promoters are well conserved and contain putative binding sites for AP1 and SP1 at positions (-94) - (-85) and (-54) - (-47), respectively. Moreover, recent studies of the rat promoter have demonstrated the presence of additional trans-acting factors at conserved sequences. The functional significance of the c/s-elements was investigated by transient expression of CCK-CAT deletion constructs of the region (-1400) - (-1). Deletions of sequences upstream of -248 increased CAT activity -5 times. Maximal CAT activity was observed with constructs containing the AP1 palindrome (-94) - (-85). In contrast, only low CAT activity was obtained with promoter sequences downstream of position (-67). The results suggest that Fos and Jun which constitute the AP1 complex are major regulatory factors of the CCK gene, however, additional trans-acting factors may be present and experiments addressing this are currently underway.
TRANSCRIPTIONAL CONTROL OF T H E HUMAN CHOLECYSTOKININ GENE. Pedersen K, Nielsen FC, Rehfeld JF. Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Cholecystokinin (CCK) belongs to the gastrin/CCK family of regulatory peptides in the brain and gut. The CCK gene is expressed in a tissue specific and developmentally regulated manner, and the aim of the present study is to characterize the c/s and transacting elements which control transcription of the human CCK gene. The CCK promoter was cloned from human neuroblastoma SK-N-MC cells. A comparison of the rat and human sequences shows that the two promoters are well conserved and contain putative binding sites for AP1 and SP1 at positions (-94) - (-85) and (-54) - (-47), respectively. Moreover, recent studies of the rat promoter have demonstrated the presence of additional trans-acting factors at conserved sequences. The functional significance of the c/s-elements was investigated by transient expression of CCK-CAT deletion constructs of the region (-1400) - (-1). Deletions of sequences upstream of -248 increased CAT activity -5 times. Maximal CAT activity was observed with constructs containing the AP1 palindrome (-94) - (-85). In contrast, only low CAT activity was obtained with promoter sequences downstream of position (-67). The results suggest that Fos and Jun which constitute the AP1 complex are major regulatory factors of the CCK gene, however, additional trans-acting factors may be present and experiments addressing this are currently underway.