Retinoic acid-dependent transforming growth factor-β2-mediated induction of MUC4 mucin expression in human pancreatic tumor cells follows retinoic acid receptor-α signaling pathway

Amit Choudhury, Rakesh K Singh, Nicolas Moniaux, Tarek H. El-Metwally, Jean Pierre Aubert, Surinder Kumar Batra

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The MUC4 mucin is considered as the homologue of rat sialomucin complex (SMC, rat Muc4) due to its similar structural organization. Like SMC, MUC4 may also exist as two subunits: A mucin type unit known as MUC4α and a growth factor-like transmembrane subunit, MUC4β. The expression of MUC4 in normal human pancreas is not detectable, but it is highly expressed in pancreatic tumor cells. In the present study, we investigated the regulation of MUC4 expression in human pancreatic tumor cells CD18/HPAF, exhibiting a high level of MUC4 transcripts and protein. When these cells were adapted to grow in the serum-free medium (CD18/HPAFSF), the MUC4 expression was undetectable. Among several serum constituents, all-trans-retinoic acid (RA) induced the expression of MUC4 transcripts in a concentration- and time-dependent manner. The RA-mediated increase in the level of the MUC4 transcript coincided with an increased expression of transforming growth factor-β2 (TGF-β2) transcript. The antagonist of the retinoic acid receptor (RAR)-α (Ro41-5253) abrogated the expression of MUC4 and TGF-β2 induced by RA. The exogenous addition of TGF-β2 also increased the MUC4 expression. The TGF-β-neutralizing antibody blocked the RA-induced as well as TGF-β2-mediated MUC4 expression. In conclusion, induction of MUC4 expression in pancreatic carcinoma by RA is mediated through the RAR-α signaling pathway, and TGF-β2 may serve as an interim mediator of this regulated expression.

Original languageEnglish (US)
Pages (from-to)33929-33936
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number43
DOIs
StatePublished - Oct 27 2000

Fingerprint

Retinoic Acid Receptors
Transforming Growth Factors
Mucins
Tretinoin
Tumors
Cells
Neoplasms
Rats
Sialomucins
Serum-Free Culture Media
Neutralizing Antibodies
Pancreas
Intercellular Signaling Peptides and Proteins
Serum
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Retinoic acid-dependent transforming growth factor-β2-mediated induction of MUC4 mucin expression in human pancreatic tumor cells follows retinoic acid receptor-α signaling pathway. / Choudhury, Amit; Singh, Rakesh K; Moniaux, Nicolas; El-Metwally, Tarek H.; Aubert, Jean Pierre; Batra, Surinder Kumar.

In: Journal of Biological Chemistry, Vol. 275, No. 43, 27.10.2000, p. 33929-33936.

Research output: Contribution to journalArticle

@article{af8883b2c7f84abe8b125c0916ea5988,
title = "Retinoic acid-dependent transforming growth factor-β2-mediated induction of MUC4 mucin expression in human pancreatic tumor cells follows retinoic acid receptor-α signaling pathway",
abstract = "The MUC4 mucin is considered as the homologue of rat sialomucin complex (SMC, rat Muc4) due to its similar structural organization. Like SMC, MUC4 may also exist as two subunits: A mucin type unit known as MUC4α and a growth factor-like transmembrane subunit, MUC4β. The expression of MUC4 in normal human pancreas is not detectable, but it is highly expressed in pancreatic tumor cells. In the present study, we investigated the regulation of MUC4 expression in human pancreatic tumor cells CD18/HPAF, exhibiting a high level of MUC4 transcripts and protein. When these cells were adapted to grow in the serum-free medium (CD18/HPAFSF), the MUC4 expression was undetectable. Among several serum constituents, all-trans-retinoic acid (RA) induced the expression of MUC4 transcripts in a concentration- and time-dependent manner. The RA-mediated increase in the level of the MUC4 transcript coincided with an increased expression of transforming growth factor-β2 (TGF-β2) transcript. The antagonist of the retinoic acid receptor (RAR)-α (Ro41-5253) abrogated the expression of MUC4 and TGF-β2 induced by RA. The exogenous addition of TGF-β2 also increased the MUC4 expression. The TGF-β-neutralizing antibody blocked the RA-induced as well as TGF-β2-mediated MUC4 expression. In conclusion, induction of MUC4 expression in pancreatic carcinoma by RA is mediated through the RAR-α signaling pathway, and TGF-β2 may serve as an interim mediator of this regulated expression.",
author = "Amit Choudhury and Singh, {Rakesh K} and Nicolas Moniaux and El-Metwally, {Tarek H.} and Aubert, {Jean Pierre} and Batra, {Surinder Kumar}",
year = "2000",
month = "10",
day = "27",
doi = "10.1074/jbc.M005115200",
language = "English (US)",
volume = "275",
pages = "33929--33936",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "43",

}

TY - JOUR

T1 - Retinoic acid-dependent transforming growth factor-β2-mediated induction of MUC4 mucin expression in human pancreatic tumor cells follows retinoic acid receptor-α signaling pathway

AU - Choudhury, Amit

AU - Singh, Rakesh K

AU - Moniaux, Nicolas

AU - El-Metwally, Tarek H.

AU - Aubert, Jean Pierre

AU - Batra, Surinder Kumar

PY - 2000/10/27

Y1 - 2000/10/27

N2 - The MUC4 mucin is considered as the homologue of rat sialomucin complex (SMC, rat Muc4) due to its similar structural organization. Like SMC, MUC4 may also exist as two subunits: A mucin type unit known as MUC4α and a growth factor-like transmembrane subunit, MUC4β. The expression of MUC4 in normal human pancreas is not detectable, but it is highly expressed in pancreatic tumor cells. In the present study, we investigated the regulation of MUC4 expression in human pancreatic tumor cells CD18/HPAF, exhibiting a high level of MUC4 transcripts and protein. When these cells were adapted to grow in the serum-free medium (CD18/HPAFSF), the MUC4 expression was undetectable. Among several serum constituents, all-trans-retinoic acid (RA) induced the expression of MUC4 transcripts in a concentration- and time-dependent manner. The RA-mediated increase in the level of the MUC4 transcript coincided with an increased expression of transforming growth factor-β2 (TGF-β2) transcript. The antagonist of the retinoic acid receptor (RAR)-α (Ro41-5253) abrogated the expression of MUC4 and TGF-β2 induced by RA. The exogenous addition of TGF-β2 also increased the MUC4 expression. The TGF-β-neutralizing antibody blocked the RA-induced as well as TGF-β2-mediated MUC4 expression. In conclusion, induction of MUC4 expression in pancreatic carcinoma by RA is mediated through the RAR-α signaling pathway, and TGF-β2 may serve as an interim mediator of this regulated expression.

AB - The MUC4 mucin is considered as the homologue of rat sialomucin complex (SMC, rat Muc4) due to its similar structural organization. Like SMC, MUC4 may also exist as two subunits: A mucin type unit known as MUC4α and a growth factor-like transmembrane subunit, MUC4β. The expression of MUC4 in normal human pancreas is not detectable, but it is highly expressed in pancreatic tumor cells. In the present study, we investigated the regulation of MUC4 expression in human pancreatic tumor cells CD18/HPAF, exhibiting a high level of MUC4 transcripts and protein. When these cells were adapted to grow in the serum-free medium (CD18/HPAFSF), the MUC4 expression was undetectable. Among several serum constituents, all-trans-retinoic acid (RA) induced the expression of MUC4 transcripts in a concentration- and time-dependent manner. The RA-mediated increase in the level of the MUC4 transcript coincided with an increased expression of transforming growth factor-β2 (TGF-β2) transcript. The antagonist of the retinoic acid receptor (RAR)-α (Ro41-5253) abrogated the expression of MUC4 and TGF-β2 induced by RA. The exogenous addition of TGF-β2 also increased the MUC4 expression. The TGF-β-neutralizing antibody blocked the RA-induced as well as TGF-β2-mediated MUC4 expression. In conclusion, induction of MUC4 expression in pancreatic carcinoma by RA is mediated through the RAR-α signaling pathway, and TGF-β2 may serve as an interim mediator of this regulated expression.

UR - http://www.scopus.com/inward/record.url?scp=0034721852&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034721852&partnerID=8YFLogxK

U2 - 10.1074/jbc.M005115200

DO - 10.1074/jbc.M005115200

M3 - Article

C2 - 10938282

AN - SCOPUS:0034721852

VL - 275

SP - 33929

EP - 33936

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 43

ER -