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Differential expression of transforming growth factor beta receptors in human pancreatic adenocarcinoma.
Anticancer Res 2000 Jan-Feb; 20(1A):43-51AR

Abstract

BACKGROUND

Many cancer cells show resistance to transforming growth factor beta (TGF-beta)-mediated growth inhibition. This resistance to TGF-beta is associated with an increased tumorigenic phenotype.

OBJECTIVE

In this study, we determined whether a loss in expression of TGF-beta receptors or DPC4, an important down stream target of TGF-beta signaling, might account for this lack of TGF-beta sensitivity in pancreatic adenocarcinoma.

MATERIALS AND METHODS

To accomplish this, six established pancreatic cancer cell lines, twenty-six surgically resected tumor specimens of pancreatic adenocarcinoma and ten non-tumor pancreas tissues were analyzed for the mRNA expression of the three TGF-beta receptors (RI, RII, and RIII) and DPC4.

RESULTS

We report here that five of six pancreatic cancer cell lines were not sensitive to TGF-beta. All the ten non-tumor specimens of pancreas showed expression of RI, and DPC4; while nine of ten showed expression of RIII and eight of ten showed expression of RII. Five of six pancreatic cancer cell lines and 23 of 26 tumor specimens showed expression of RI. Two cell lines and about half (46%) of the tumor specimens did not express RII. Only two cell lines showed appreciable levels of RIII expression; while ten of 26 (38%) tumor specimens did not show expression of RIII. DPC4 expression was observed in three of the six (50%) cell lines and 19 of 24 (79%) tumor specimens.

CONCLUSION

This study indicates that apart from the functional loss of DPC4 due to mutations or homozygous deletion, a lack of the TGF-beta receptors, particularly RII and RIII, may contribute to a loss of TGF-beta signaling in a population of pancreatic cancers.

Authors+Show Affiliations

Department of Surgery, University of Texas Health Science Center, San Antonio 78284, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10769633

Citation

Venkatasubbarao, K, et al. "Differential Expression of Transforming Growth Factor Beta Receptors in Human Pancreatic Adenocarcinoma." Anticancer Research, vol. 20, no. 1A, 2000, pp. 43-51.
Venkatasubbarao K, Ahmed MM, Mohiuddin M, et al. Differential expression of transforming growth factor beta receptors in human pancreatic adenocarcinoma. Anticancer Res. 2000;20(1A):43-51.
Venkatasubbarao, K., Ahmed, M. M., Mohiuddin, M., Swiderski, C., Lee, E., Gower, W. R., ... Freeman, J. W. (2000). Differential expression of transforming growth factor beta receptors in human pancreatic adenocarcinoma. Anticancer Research, 20(1A), pp. 43-51.
Venkatasubbarao K, et al. Differential Expression of Transforming Growth Factor Beta Receptors in Human Pancreatic Adenocarcinoma. Anticancer Res. 2000;20(1A):43-51. PubMed PMID: 10769633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential expression of transforming growth factor beta receptors in human pancreatic adenocarcinoma. AU - Venkatasubbarao,K, AU - Ahmed,M M, AU - Mohiuddin,M, AU - Swiderski,C, AU - Lee,E, AU - Gower,W R,Jr AU - Salhab,K F, AU - McGrath,P, AU - Strodel,W, AU - Freeman,J W, PY - 2000/4/19/pubmed PY - 2000/5/16/medline PY - 2000/4/19/entrez SP - 43 EP - 51 JF - Anticancer research JO - Anticancer Res. VL - 20 IS - 1A N2 - BACKGROUND: Many cancer cells show resistance to transforming growth factor beta (TGF-beta)-mediated growth inhibition. This resistance to TGF-beta is associated with an increased tumorigenic phenotype. OBJECTIVE: In this study, we determined whether a loss in expression of TGF-beta receptors or DPC4, an important down stream target of TGF-beta signaling, might account for this lack of TGF-beta sensitivity in pancreatic adenocarcinoma. MATERIALS AND METHODS: To accomplish this, six established pancreatic cancer cell lines, twenty-six surgically resected tumor specimens of pancreatic adenocarcinoma and ten non-tumor pancreas tissues were analyzed for the mRNA expression of the three TGF-beta receptors (RI, RII, and RIII) and DPC4. RESULTS: We report here that five of six pancreatic cancer cell lines were not sensitive to TGF-beta. All the ten non-tumor specimens of pancreas showed expression of RI, and DPC4; while nine of ten showed expression of RIII and eight of ten showed expression of RII. Five of six pancreatic cancer cell lines and 23 of 26 tumor specimens showed expression of RI. Two cell lines and about half (46%) of the tumor specimens did not express RII. Only two cell lines showed appreciable levels of RIII expression; while ten of 26 (38%) tumor specimens did not show expression of RIII. DPC4 expression was observed in three of the six (50%) cell lines and 19 of 24 (79%) tumor specimens. CONCLUSION: This study indicates that apart from the functional loss of DPC4 due to mutations or homozygous deletion, a lack of the TGF-beta receptors, particularly RII and RIII, may contribute to a loss of TGF-beta signaling in a population of pancreatic cancers. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/10769633/Differential_expression_of_transforming_growth_factor_beta_receptors_in_human_pancreatic_adenocarcinoma_ L2 - https://medlineplus.gov/pancreaticcancer.html DB - PRIME DP - Unbound Medicine ER -