Auto-induction and growth stimulatory effect of betacellulin in human pancreatic cancer cells.

M. Kawaguchi, R. Hosotani, M. Kogire, J. Ida, R. Doi, T. Koshiba, Y. Miyamoto, Shoichiro Tsuji, S. Nakajima, H. Kobayashi, T. Masui, M. Imamura

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Betacellulin (BTC) was identified in mouse pancreatic beta cell tumors as a member of the epidermal growth factor (EGF) family, and was found to bind and activate the EGF receptor. BTC is also expressed in some human malignancies and may have an important role in tumor growth progression. We examined whether BTC and EGF have a growth stimulatory effect on human pancreatic cancer cell lines both in vitro and in vivo. We also investigated the BTC expression and autonomous induction of BTC in pancreatic cancer cells. in vitro, both BTC and EGF had almost the same proliferative effect on Panc-1, MIA PaCa-2 and AsPC-1. in vivo, in a Panc-1 inoculated athymic mice model, BTC-treated tumors grew approximately five times larger than in control. Immunocytochemistry showed that BTC expression occurred in three pancreatic cancer cell lines, with MIA PaCa-2 showing the strongest intensity. Semi-quantitative RT-PCR of MIA Paca-2 showed that mRNA levels of BTC gradually increased after treatment with 1 nM BTC. Immunocytochemistry also demonstrated that the intensity of BTC-like immunoreactivity was increased when treated with 1 nM BTC but was reduced after treatment with 100 nM of AG1478, an EGF receptor tyrosine kinase inhibitor. BTC has thus a significant growth stimulatory effect on pancreatic cancer cells and might function as an autocrine and paracrine growth factor. BTC expression in pancreatic cancer cells is, at least in part, controlled by an auto-induction mechanism.

Original languageEnglish
Pages (from-to)37-41
Number of pages5
JournalInternational Journal of Oncology
Volume16
Issue number1
Publication statusPublished - 01-01-2000

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Pancreatic Neoplasms
Growth
Epidermal Growth Factor
Betacellulin
Epidermal Growth Factor Receptor
Immunohistochemistry
Cell Line
Neoplasms
Insulinoma
Insulin-Secreting Cells
Nude Mice
Protein-Tyrosine Kinases
Intercellular Signaling Peptides and Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kawaguchi, M., Hosotani, R., Kogire, M., Ida, J., Doi, R., Koshiba, T., ... Imamura, M. (2000). Auto-induction and growth stimulatory effect of betacellulin in human pancreatic cancer cells. International Journal of Oncology, 16(1), 37-41.
Kawaguchi, M. ; Hosotani, R. ; Kogire, M. ; Ida, J. ; Doi, R. ; Koshiba, T. ; Miyamoto, Y. ; Tsuji, Shoichiro ; Nakajima, S. ; Kobayashi, H. ; Masui, T. ; Imamura, M. / Auto-induction and growth stimulatory effect of betacellulin in human pancreatic cancer cells. In: International Journal of Oncology. 2000 ; Vol. 16, No. 1. pp. 37-41.
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abstract = "Betacellulin (BTC) was identified in mouse pancreatic beta cell tumors as a member of the epidermal growth factor (EGF) family, and was found to bind and activate the EGF receptor. BTC is also expressed in some human malignancies and may have an important role in tumor growth progression. We examined whether BTC and EGF have a growth stimulatory effect on human pancreatic cancer cell lines both in vitro and in vivo. We also investigated the BTC expression and autonomous induction of BTC in pancreatic cancer cells. in vitro, both BTC and EGF had almost the same proliferative effect on Panc-1, MIA PaCa-2 and AsPC-1. in vivo, in a Panc-1 inoculated athymic mice model, BTC-treated tumors grew approximately five times larger than in control. Immunocytochemistry showed that BTC expression occurred in three pancreatic cancer cell lines, with MIA PaCa-2 showing the strongest intensity. Semi-quantitative RT-PCR of MIA Paca-2 showed that mRNA levels of BTC gradually increased after treatment with 1 nM BTC. Immunocytochemistry also demonstrated that the intensity of BTC-like immunoreactivity was increased when treated with 1 nM BTC but was reduced after treatment with 100 nM of AG1478, an EGF receptor tyrosine kinase inhibitor. BTC has thus a significant growth stimulatory effect on pancreatic cancer cells and might function as an autocrine and paracrine growth factor. BTC expression in pancreatic cancer cells is, at least in part, controlled by an auto-induction mechanism.",
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Kawaguchi, M, Hosotani, R, Kogire, M, Ida, J, Doi, R, Koshiba, T, Miyamoto, Y, Tsuji, S, Nakajima, S, Kobayashi, H, Masui, T & Imamura, M 2000, 'Auto-induction and growth stimulatory effect of betacellulin in human pancreatic cancer cells.', International Journal of Oncology, vol. 16, no. 1, pp. 37-41.

Auto-induction and growth stimulatory effect of betacellulin in human pancreatic cancer cells. / Kawaguchi, M.; Hosotani, R.; Kogire, M.; Ida, J.; Doi, R.; Koshiba, T.; Miyamoto, Y.; Tsuji, Shoichiro; Nakajima, S.; Kobayashi, H.; Masui, T.; Imamura, M.

In: International Journal of Oncology, Vol. 16, No. 1, 01.01.2000, p. 37-41.

Research output: Contribution to journalArticle

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T1 - Auto-induction and growth stimulatory effect of betacellulin in human pancreatic cancer cells.

AU - Kawaguchi, M.

AU - Hosotani, R.

AU - Kogire, M.

AU - Ida, J.

AU - Doi, R.

AU - Koshiba, T.

AU - Miyamoto, Y.

AU - Tsuji, Shoichiro

AU - Nakajima, S.

AU - Kobayashi, H.

AU - Masui, T.

AU - Imamura, M.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Betacellulin (BTC) was identified in mouse pancreatic beta cell tumors as a member of the epidermal growth factor (EGF) family, and was found to bind and activate the EGF receptor. BTC is also expressed in some human malignancies and may have an important role in tumor growth progression. We examined whether BTC and EGF have a growth stimulatory effect on human pancreatic cancer cell lines both in vitro and in vivo. We also investigated the BTC expression and autonomous induction of BTC in pancreatic cancer cells. in vitro, both BTC and EGF had almost the same proliferative effect on Panc-1, MIA PaCa-2 and AsPC-1. in vivo, in a Panc-1 inoculated athymic mice model, BTC-treated tumors grew approximately five times larger than in control. Immunocytochemistry showed that BTC expression occurred in three pancreatic cancer cell lines, with MIA PaCa-2 showing the strongest intensity. Semi-quantitative RT-PCR of MIA Paca-2 showed that mRNA levels of BTC gradually increased after treatment with 1 nM BTC. Immunocytochemistry also demonstrated that the intensity of BTC-like immunoreactivity was increased when treated with 1 nM BTC but was reduced after treatment with 100 nM of AG1478, an EGF receptor tyrosine kinase inhibitor. BTC has thus a significant growth stimulatory effect on pancreatic cancer cells and might function as an autocrine and paracrine growth factor. BTC expression in pancreatic cancer cells is, at least in part, controlled by an auto-induction mechanism.

AB - Betacellulin (BTC) was identified in mouse pancreatic beta cell tumors as a member of the epidermal growth factor (EGF) family, and was found to bind and activate the EGF receptor. BTC is also expressed in some human malignancies and may have an important role in tumor growth progression. We examined whether BTC and EGF have a growth stimulatory effect on human pancreatic cancer cell lines both in vitro and in vivo. We also investigated the BTC expression and autonomous induction of BTC in pancreatic cancer cells. in vitro, both BTC and EGF had almost the same proliferative effect on Panc-1, MIA PaCa-2 and AsPC-1. in vivo, in a Panc-1 inoculated athymic mice model, BTC-treated tumors grew approximately five times larger than in control. Immunocytochemistry showed that BTC expression occurred in three pancreatic cancer cell lines, with MIA PaCa-2 showing the strongest intensity. Semi-quantitative RT-PCR of MIA Paca-2 showed that mRNA levels of BTC gradually increased after treatment with 1 nM BTC. Immunocytochemistry also demonstrated that the intensity of BTC-like immunoreactivity was increased when treated with 1 nM BTC but was reduced after treatment with 100 nM of AG1478, an EGF receptor tyrosine kinase inhibitor. BTC has thus a significant growth stimulatory effect on pancreatic cancer cells and might function as an autocrine and paracrine growth factor. BTC expression in pancreatic cancer cells is, at least in part, controlled by an auto-induction mechanism.

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Kawaguchi M, Hosotani R, Kogire M, Ida J, Doi R, Koshiba T et al. Auto-induction and growth stimulatory effect of betacellulin in human pancreatic cancer cells. International Journal of Oncology. 2000 Jan 1;16(1):37-41.