HPAC, a new human glucocorticoid-sensitive pancreatic ductal adenocarcinoma cell line.
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 384862 Binding of [3H] dexamethasone to cytosolic proteins was specific and saturable at 4 degrees C. Scatchard analysis of binding data demonstrated a single class of high-affinity binding sites (K(d) = 3.8 ± 0.9 nM; B(max) = 523 ± 128 fmol/mg protein). Western blot analysis revealed a major protein band that migrated at a M(r) 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.
Laboratory Service, James A. Haley Veterans Hospital, Tampa, Florida 33612, USA.
W R
WR
Gower
R M
RM
Risch
C V
CV
Godellas
P J
PJ
Fabri
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D059785:Karyotype; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015735:Mifepristone / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D006727:Hormone Antagonists; D007328:Insulin; D011965:Receptors, Glucocorticoid; D016211:Transforming Growth Factor alpha; D015735:Mifepristone; D003907:Dexamethasone; D006854:Hydrocortisone