HPAC,a new human glucocorticoid-sensitive pancreatic ductal adenocarcinoma cell line |
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Authors: | William R Gower Jr Robert M Risch Constantine V Godellas Peter J Fabri |
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Institution: | (1) James A. Haley Veterans Hospital, Research Service (151), 13000 Bruce B. Downs Blvd., 33612 Tampa, Florida;(2) Laboratory, James A. Haley Veterans Hospital, USA;(3) Surgery Services, James A. Haley Veterans Hospital, USA;(4) Department of Biochemistry and Molecular Biology, University of South Florida, College of Medicine, 33612 Tampa, Florida;(5) Department of Surgery, University of South Florida, College of Medicine, 33612 Tampa, Florida |
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Abstract: | Summary A new human pancreatic cancer (HPAC) cell line was established from a nude mouse xenograft (CAP) of a primary human pancreatic
ductal adenocarcinoma. In culture, HPAC cells form monolayers of morphologically heterogenous, polar epithelial cells, which
synthesize carcinoembryonic antigen, CA 19-9, CA-125, cytokeratins, antigens for DU-PAN-2, HMFG1, and AUA1, but do not express
chromogranin A or vimentin indicative of their pancreatic ductal epithelial cell character. In the presence of serum, HPAC
cell DNA synthesis was stimulated by insulin, insulin growth factor-I, epidermal growth factor, and TGF-α but inhibited
by physiologic concentrations of hydrocortisone and dexamethasone. Dose-dependent inhibition of DNA synthesis was limited
to steroids with glucocorticoid activity. The inhibitory effect of dexamethasone was abolished by the glucocorticoid antagonist
RU 38486. Binding of 3H]dexamethasone to cytosolic proteins was specific and saturable at 4° C. Scatchard analysis of binding data demonstrated
a single class of high-affinity binding sites (Kd=3.8±0.9 nM; Bmax=523±128 fmol/mg protein). Western blot analysis revealed a major protein band that migrated at a Mr of 96 kDa. Northern blot analysis identified an mRNA of approximately 7 kilobases which hybridized with a specific glucocorticoid
receptor complementary DNA probe (OB7). These findings support a role for glucocorticoids in the regulation of human malignant
pancreatic cell function. |
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Keywords: | pancreatic cancer glucocorticoids growth inhibition glucocorticoid receptor dexamethasone |
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