Phorbol ester-induced alteration in the pattern of secretion and storage of chromogranin A and neurotensin in a human pancreatic carcinoid cell line

T. Zhang, Courtney Townsend, V. Udupi, N. Yanaihara, S. Rajaraman, R. D. Beauchamp, J. Ishizuka, B. M. Evers, Guillermo Gomez, J. C. Thompson, G. H. Greeley

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Abstract

Brief phorbol ester treatment of BON cells results in a persistent release and cellular depletion of immunoreactive chromogranin A (CGA-IR) and neurotensin (NT-IR) cell contents. The purpose of the present study was to characterize the effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on the secretion, biosynthesis, and steady-state messenger RNA (mRNA) levels of chromogranin A (CGA) and of a coresident peptide, neurotensin, by a novel human pancreatic carcinoid cell line, called BON. Acute TPA treatment (100 nM, 1 h) of BON cells resulted in 20- and 40-fold elevations in release of CGA-IR and NT-IR, respectively; and a 70-90% depletion of CGA-IR and NT-IR cell contents. TPA treatment also increased the biosynthetic rate of CGA-IR. Steady-state mRNA levels of CGA and NT/N (neurotensin/neuromedin N) were unchanged. Cell contents of CGA-IR and NT-IR were not replenished for a period of up to 6 days; secretion of CGA-IR and NT-IR persisted. In addition, BON cells failed to release CGA in response to stimulation by ionomycin and A23187 several days after acute TPA treatment. Our data indicate that the lack of replenishment of cell contents of CGA-IR and NT-IR is not due to decreases in steady-state CGA-IR and NT-IR mRNA levels, nor is it due to a decrease in biosynthesis of CGA-IR, but it is the result of a loss in the ability of TPA-treated BON cells to store and secrete CGA-IR and NT-IR in a regulated manner. These effects of TPA are radiated through the PKC pathway.

Original languageEnglish (US)
Pages (from-to)2252-2261
Number of pages10
JournalEndocrinology
Volume136
Issue number5
StatePublished - 1995

Fingerprint

Chromogranin A
Neurotensin
Carcinoid Tumor
Phorbol Esters
Cell Line
Tetradecanoylphorbol Acetate
neuromedin N
Messenger RNA
Ionomycin
Calcimycin

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Zhang, T., Townsend, C., Udupi, V., Yanaihara, N., Rajaraman, S., Beauchamp, R. D., ... Greeley, G. H. (1995). Phorbol ester-induced alteration in the pattern of secretion and storage of chromogranin A and neurotensin in a human pancreatic carcinoid cell line. Endocrinology, 136(5), 2252-2261.

Phorbol ester-induced alteration in the pattern of secretion and storage of chromogranin A and neurotensin in a human pancreatic carcinoid cell line. / Zhang, T.; Townsend, Courtney; Udupi, V.; Yanaihara, N.; Rajaraman, S.; Beauchamp, R. D.; Ishizuka, J.; Evers, B. M.; Gomez, Guillermo; Thompson, J. C.; Greeley, G. H.

In: Endocrinology, Vol. 136, No. 5, 1995, p. 2252-2261.

Research output: Contribution to journalArticle

Zhang, T, Townsend, C, Udupi, V, Yanaihara, N, Rajaraman, S, Beauchamp, RD, Ishizuka, J, Evers, BM, Gomez, G, Thompson, JC & Greeley, GH 1995, 'Phorbol ester-induced alteration in the pattern of secretion and storage of chromogranin A and neurotensin in a human pancreatic carcinoid cell line', Endocrinology, vol. 136, no. 5, pp. 2252-2261.
Zhang, T. ; Townsend, Courtney ; Udupi, V. ; Yanaihara, N. ; Rajaraman, S. ; Beauchamp, R. D. ; Ishizuka, J. ; Evers, B. M. ; Gomez, Guillermo ; Thompson, J. C. ; Greeley, G. H. / Phorbol ester-induced alteration in the pattern of secretion and storage of chromogranin A and neurotensin in a human pancreatic carcinoid cell line. In: Endocrinology. 1995 ; Vol. 136, No. 5. pp. 2252-2261.
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abstract = "Brief phorbol ester treatment of BON cells results in a persistent release and cellular depletion of immunoreactive chromogranin A (CGA-IR) and neurotensin (NT-IR) cell contents. The purpose of the present study was to characterize the effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on the secretion, biosynthesis, and steady-state messenger RNA (mRNA) levels of chromogranin A (CGA) and of a coresident peptide, neurotensin, by a novel human pancreatic carcinoid cell line, called BON. Acute TPA treatment (100 nM, 1 h) of BON cells resulted in 20- and 40-fold elevations in release of CGA-IR and NT-IR, respectively; and a 70-90{\%} depletion of CGA-IR and NT-IR cell contents. TPA treatment also increased the biosynthetic rate of CGA-IR. Steady-state mRNA levels of CGA and NT/N (neurotensin/neuromedin N) were unchanged. Cell contents of CGA-IR and NT-IR were not replenished for a period of up to 6 days; secretion of CGA-IR and NT-IR persisted. In addition, BON cells failed to release CGA in response to stimulation by ionomycin and A23187 several days after acute TPA treatment. Our data indicate that the lack of replenishment of cell contents of CGA-IR and NT-IR is not due to decreases in steady-state CGA-IR and NT-IR mRNA levels, nor is it due to a decrease in biosynthesis of CGA-IR, but it is the result of a loss in the ability of TPA-treated BON cells to store and secrete CGA-IR and NT-IR in a regulated manner. These effects of TPA are radiated through the PKC pathway.",
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AU - Zhang, T.

AU - Townsend, Courtney

AU - Udupi, V.

AU - Yanaihara, N.

AU - Rajaraman, S.

AU - Beauchamp, R. D.

AU - Ishizuka, J.

AU - Evers, B. M.

AU - Gomez, Guillermo

AU - Thompson, J. C.

AU - Greeley, G. H.

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N2 - Brief phorbol ester treatment of BON cells results in a persistent release and cellular depletion of immunoreactive chromogranin A (CGA-IR) and neurotensin (NT-IR) cell contents. The purpose of the present study was to characterize the effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on the secretion, biosynthesis, and steady-state messenger RNA (mRNA) levels of chromogranin A (CGA) and of a coresident peptide, neurotensin, by a novel human pancreatic carcinoid cell line, called BON. Acute TPA treatment (100 nM, 1 h) of BON cells resulted in 20- and 40-fold elevations in release of CGA-IR and NT-IR, respectively; and a 70-90% depletion of CGA-IR and NT-IR cell contents. TPA treatment also increased the biosynthetic rate of CGA-IR. Steady-state mRNA levels of CGA and NT/N (neurotensin/neuromedin N) were unchanged. Cell contents of CGA-IR and NT-IR were not replenished for a period of up to 6 days; secretion of CGA-IR and NT-IR persisted. In addition, BON cells failed to release CGA in response to stimulation by ionomycin and A23187 several days after acute TPA treatment. Our data indicate that the lack of replenishment of cell contents of CGA-IR and NT-IR is not due to decreases in steady-state CGA-IR and NT-IR mRNA levels, nor is it due to a decrease in biosynthesis of CGA-IR, but it is the result of a loss in the ability of TPA-treated BON cells to store and secrete CGA-IR and NT-IR in a regulated manner. These effects of TPA are radiated through the PKC pathway.

AB - Brief phorbol ester treatment of BON cells results in a persistent release and cellular depletion of immunoreactive chromogranin A (CGA-IR) and neurotensin (NT-IR) cell contents. The purpose of the present study was to characterize the effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on the secretion, biosynthesis, and steady-state messenger RNA (mRNA) levels of chromogranin A (CGA) and of a coresident peptide, neurotensin, by a novel human pancreatic carcinoid cell line, called BON. Acute TPA treatment (100 nM, 1 h) of BON cells resulted in 20- and 40-fold elevations in release of CGA-IR and NT-IR, respectively; and a 70-90% depletion of CGA-IR and NT-IR cell contents. TPA treatment also increased the biosynthetic rate of CGA-IR. Steady-state mRNA levels of CGA and NT/N (neurotensin/neuromedin N) were unchanged. Cell contents of CGA-IR and NT-IR were not replenished for a period of up to 6 days; secretion of CGA-IR and NT-IR persisted. In addition, BON cells failed to release CGA in response to stimulation by ionomycin and A23187 several days after acute TPA treatment. Our data indicate that the lack of replenishment of cell contents of CGA-IR and NT-IR is not due to decreases in steady-state CGA-IR and NT-IR mRNA levels, nor is it due to a decrease in biosynthesis of CGA-IR, but it is the result of a loss in the ability of TPA-treated BON cells to store and secrete CGA-IR and NT-IR in a regulated manner. These effects of TPA are radiated through the PKC pathway.

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