The essential similarity of TGFβ and activin receptor transcriptional responses in cancer cells

Byungwoo Ryu, Scott E Kern

Research output: Contribution to journalArticle

Abstract

The binding of activin and TGFβ to their respective receptors initiates signals that are carried by common intermediates (Smad proteins) to induce transcriptional activation of downstream genes. Mutations in tumors indicate that both receptor types convey tumor-suppressive signals, among other biologic roles, but their respective sets of transcriptional targets (transcriptomes) and the shared degree of transcriptome similarity are not well explored in these cells. Transcriptome changes were analyzed by gene expression profiling after expression of constitutively active activin type I (ALK4m) and TGFβ type I (ALK5m) receptors and by variation of Smad4 expression in cancer cells. Eleven of 15 previously reported TGFβ downstream genes were confirmed to be responsive to TGFb and activin receptors in cancer cells. Expression profiling detected eight of these 11, as well as 13 new Smad4-dependent transcripts. Although Smad4-dependent CDKN1A/p21 induction represents the sole known effector of TGFβ and activin tumor-suppressor effects, many downstream genes have not yet been evaluated for a suppressive role. A high similarity of TGFβ and activin responses among the known and new transcriptional target genes indicated an essential redundancy of the two related inputs. This similarity helps relate the mutations seen in both receptor systems and their Smad mediators in human cancers.

Original languageEnglish (US)
Pages (from-to)164-170
Number of pages7
JournalCancer Biology and Therapy
Volume2
Issue number2
DOIs
StatePublished - Mar 2003

Fingerprint

Activin Receptors
Activins
Transcriptome
Neoplasms
Smad4 Protein
Smad Proteins
Genes
Mutation
Essential Genes
Gene Expression Profiling
Transcriptional Activation

Keywords

  • Activin
  • Gene expression profiling
  • Pancreatic cancer
  • Signal transduction
  • Transforming growth factor beta

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

The essential similarity of TGFβ and activin receptor transcriptional responses in cancer cells. / Ryu, Byungwoo; Kern, Scott E.

In: Cancer Biology and Therapy, Vol. 2, No. 2, 03.2003, p. 164-170.

Research output: Contribution to journalArticle

@article{59289165897441a4b04200d5918d0df6,
title = "The essential similarity of TGFβ and activin receptor transcriptional responses in cancer cells",
abstract = "The binding of activin and TGFβ to their respective receptors initiates signals that are carried by common intermediates (Smad proteins) to induce transcriptional activation of downstream genes. Mutations in tumors indicate that both receptor types convey tumor-suppressive signals, among other biologic roles, but their respective sets of transcriptional targets (transcriptomes) and the shared degree of transcriptome similarity are not well explored in these cells. Transcriptome changes were analyzed by gene expression profiling after expression of constitutively active activin type I (ALK4m) and TGFβ type I (ALK5m) receptors and by variation of Smad4 expression in cancer cells. Eleven of 15 previously reported TGFβ downstream genes were confirmed to be responsive to TGFb and activin receptors in cancer cells. Expression profiling detected eight of these 11, as well as 13 new Smad4-dependent transcripts. Although Smad4-dependent CDKN1A/p21 induction represents the sole known effector of TGFβ and activin tumor-suppressor effects, many downstream genes have not yet been evaluated for a suppressive role. A high similarity of TGFβ and activin responses among the known and new transcriptional target genes indicated an essential redundancy of the two related inputs. This similarity helps relate the mutations seen in both receptor systems and their Smad mediators in human cancers.",
keywords = "Activin, Gene expression profiling, Pancreatic cancer, Signal transduction, Transforming growth factor beta",
author = "Byungwoo Ryu and Kern, {Scott E}",
year = "2003",
month = "3",
doi = "10.4161/cbt.2.2.276",
language = "English (US)",
volume = "2",
pages = "164--170",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "2",

}

TY - JOUR

T1 - The essential similarity of TGFβ and activin receptor transcriptional responses in cancer cells

AU - Ryu, Byungwoo

AU - Kern, Scott E

PY - 2003/3

Y1 - 2003/3

N2 - The binding of activin and TGFβ to their respective receptors initiates signals that are carried by common intermediates (Smad proteins) to induce transcriptional activation of downstream genes. Mutations in tumors indicate that both receptor types convey tumor-suppressive signals, among other biologic roles, but their respective sets of transcriptional targets (transcriptomes) and the shared degree of transcriptome similarity are not well explored in these cells. Transcriptome changes were analyzed by gene expression profiling after expression of constitutively active activin type I (ALK4m) and TGFβ type I (ALK5m) receptors and by variation of Smad4 expression in cancer cells. Eleven of 15 previously reported TGFβ downstream genes were confirmed to be responsive to TGFb and activin receptors in cancer cells. Expression profiling detected eight of these 11, as well as 13 new Smad4-dependent transcripts. Although Smad4-dependent CDKN1A/p21 induction represents the sole known effector of TGFβ and activin tumor-suppressor effects, many downstream genes have not yet been evaluated for a suppressive role. A high similarity of TGFβ and activin responses among the known and new transcriptional target genes indicated an essential redundancy of the two related inputs. This similarity helps relate the mutations seen in both receptor systems and their Smad mediators in human cancers.

AB - The binding of activin and TGFβ to their respective receptors initiates signals that are carried by common intermediates (Smad proteins) to induce transcriptional activation of downstream genes. Mutations in tumors indicate that both receptor types convey tumor-suppressive signals, among other biologic roles, but their respective sets of transcriptional targets (transcriptomes) and the shared degree of transcriptome similarity are not well explored in these cells. Transcriptome changes were analyzed by gene expression profiling after expression of constitutively active activin type I (ALK4m) and TGFβ type I (ALK5m) receptors and by variation of Smad4 expression in cancer cells. Eleven of 15 previously reported TGFβ downstream genes were confirmed to be responsive to TGFb and activin receptors in cancer cells. Expression profiling detected eight of these 11, as well as 13 new Smad4-dependent transcripts. Although Smad4-dependent CDKN1A/p21 induction represents the sole known effector of TGFβ and activin tumor-suppressor effects, many downstream genes have not yet been evaluated for a suppressive role. A high similarity of TGFβ and activin responses among the known and new transcriptional target genes indicated an essential redundancy of the two related inputs. This similarity helps relate the mutations seen in both receptor systems and their Smad mediators in human cancers.

KW - Activin

KW - Gene expression profiling

KW - Pancreatic cancer

KW - Signal transduction

KW - Transforming growth factor beta

UR - http://www.scopus.com/inward/record.url?scp=0141872591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141872591&partnerID=8YFLogxK

U2 - 10.4161/cbt.2.2.276

DO - 10.4161/cbt.2.2.276

M3 - Article

C2 - 12750556

AN - SCOPUS:0141872591

VL - 2

SP - 164

EP - 170

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

SN - 1538-4047

IS - 2

ER -