Predominant cytosolic localization of type II transforming growth factor β receptors in human breast carcinoma cells

Katri M. Koli, Carlos L. Arteaga

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

It is proposed that loss of a growth-inhibitory response in transforming growth factor β (TGFβ) contributes to breast cancer progression. Because cellular TGFβ responsiveness often correlates with TGFβ type II receptor (TGFβ-IIR) expression, we have examined the cellular distribution of TGFβ- IIRs in tumor and nontumor mammary epithelial cells. By immunoblot analysis, TGFβ-IIR was detected both in membrane and cytosolic fractions of MDA-231 tumor cells as well as in normal human breast epithelial cells. The cytosolic protein appeared to be more abundant and was detected as a clear perinuclear staining by immunocytochemistry. The glycosylation patterns of the cytosolic and membrane form were different, indicating distinct receptor pools. The cytosolic TGFβ-IIR did not bind 125I-labeled TGFβ1 but had a detectable in vitro and in vivo kinase activity. MCF-7 breast cancer cells express the TGFβ-IIR mRNA but show undetectable cell surface TGFβ-IIR protein by affinity cross-linking. However, low levels of TGFβ-IIR were observed in MCF-7 cytosol. Sequencing of the coding region of TGFβ-IIR from MCF-7 cells indicated a point mutation (A439V) in a nonconserved region of the kinase domain. When MCF-7 cells were treated with sublethal doses of Adriamycin that induce cell differentiation, the membrane localization of TGFβ-IIR and TGFβ response were restored. Our results indicate the presence of a prominent, kinase-active TGFβ-IIR in the cytosol of several mammary cell lines. This cytosolic pool of receptors is the only detectable one in MCF-7 cells. Loss of wild-type membrane receptors due to defects in trafficking presents a potential new mechanism for escape from negative growth control.

Original languageEnglish (US)
Pages (from-to)970-977
Number of pages8
JournalCancer Research
Volume57
Issue number5
StatePublished - Mar 11 1997

Fingerprint

Growth Factor Receptors
Transforming Growth Factors
Breast Neoplasms
MCF-7 Cells
Breast
Phosphotransferases
Cytosol
Membranes
Epithelial Cells
Growth
Glycosylation
Point Mutation
Doxorubicin
Cell Differentiation
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Predominant cytosolic localization of type II transforming growth factor β receptors in human breast carcinoma cells. / Koli, Katri M.; Arteaga, Carlos L.

In: Cancer Research, Vol. 57, No. 5, 11.03.1997, p. 970-977.

Research output: Contribution to journalArticle

@article{e9fba352b7f34eb9a616a9b489c8badf,
title = "Predominant cytosolic localization of type II transforming growth factor β receptors in human breast carcinoma cells",
abstract = "It is proposed that loss of a growth-inhibitory response in transforming growth factor β (TGFβ) contributes to breast cancer progression. Because cellular TGFβ responsiveness often correlates with TGFβ type II receptor (TGFβ-IIR) expression, we have examined the cellular distribution of TGFβ- IIRs in tumor and nontumor mammary epithelial cells. By immunoblot analysis, TGFβ-IIR was detected both in membrane and cytosolic fractions of MDA-231 tumor cells as well as in normal human breast epithelial cells. The cytosolic protein appeared to be more abundant and was detected as a clear perinuclear staining by immunocytochemistry. The glycosylation patterns of the cytosolic and membrane form were different, indicating distinct receptor pools. The cytosolic TGFβ-IIR did not bind 125I-labeled TGFβ1 but had a detectable in vitro and in vivo kinase activity. MCF-7 breast cancer cells express the TGFβ-IIR mRNA but show undetectable cell surface TGFβ-IIR protein by affinity cross-linking. However, low levels of TGFβ-IIR were observed in MCF-7 cytosol. Sequencing of the coding region of TGFβ-IIR from MCF-7 cells indicated a point mutation (A439V) in a nonconserved region of the kinase domain. When MCF-7 cells were treated with sublethal doses of Adriamycin that induce cell differentiation, the membrane localization of TGFβ-IIR and TGFβ response were restored. Our results indicate the presence of a prominent, kinase-active TGFβ-IIR in the cytosol of several mammary cell lines. This cytosolic pool of receptors is the only detectable one in MCF-7 cells. Loss of wild-type membrane receptors due to defects in trafficking presents a potential new mechanism for escape from negative growth control.",
author = "Koli, {Katri M.} and Arteaga, {Carlos L.}",
year = "1997",
month = "3",
day = "11",
language = "English (US)",
volume = "57",
pages = "970--977",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - Predominant cytosolic localization of type II transforming growth factor β receptors in human breast carcinoma cells

AU - Koli, Katri M.

AU - Arteaga, Carlos L.

PY - 1997/3/11

Y1 - 1997/3/11

N2 - It is proposed that loss of a growth-inhibitory response in transforming growth factor β (TGFβ) contributes to breast cancer progression. Because cellular TGFβ responsiveness often correlates with TGFβ type II receptor (TGFβ-IIR) expression, we have examined the cellular distribution of TGFβ- IIRs in tumor and nontumor mammary epithelial cells. By immunoblot analysis, TGFβ-IIR was detected both in membrane and cytosolic fractions of MDA-231 tumor cells as well as in normal human breast epithelial cells. The cytosolic protein appeared to be more abundant and was detected as a clear perinuclear staining by immunocytochemistry. The glycosylation patterns of the cytosolic and membrane form were different, indicating distinct receptor pools. The cytosolic TGFβ-IIR did not bind 125I-labeled TGFβ1 but had a detectable in vitro and in vivo kinase activity. MCF-7 breast cancer cells express the TGFβ-IIR mRNA but show undetectable cell surface TGFβ-IIR protein by affinity cross-linking. However, low levels of TGFβ-IIR were observed in MCF-7 cytosol. Sequencing of the coding region of TGFβ-IIR from MCF-7 cells indicated a point mutation (A439V) in a nonconserved region of the kinase domain. When MCF-7 cells were treated with sublethal doses of Adriamycin that induce cell differentiation, the membrane localization of TGFβ-IIR and TGFβ response were restored. Our results indicate the presence of a prominent, kinase-active TGFβ-IIR in the cytosol of several mammary cell lines. This cytosolic pool of receptors is the only detectable one in MCF-7 cells. Loss of wild-type membrane receptors due to defects in trafficking presents a potential new mechanism for escape from negative growth control.

AB - It is proposed that loss of a growth-inhibitory response in transforming growth factor β (TGFβ) contributes to breast cancer progression. Because cellular TGFβ responsiveness often correlates with TGFβ type II receptor (TGFβ-IIR) expression, we have examined the cellular distribution of TGFβ- IIRs in tumor and nontumor mammary epithelial cells. By immunoblot analysis, TGFβ-IIR was detected both in membrane and cytosolic fractions of MDA-231 tumor cells as well as in normal human breast epithelial cells. The cytosolic protein appeared to be more abundant and was detected as a clear perinuclear staining by immunocytochemistry. The glycosylation patterns of the cytosolic and membrane form were different, indicating distinct receptor pools. The cytosolic TGFβ-IIR did not bind 125I-labeled TGFβ1 but had a detectable in vitro and in vivo kinase activity. MCF-7 breast cancer cells express the TGFβ-IIR mRNA but show undetectable cell surface TGFβ-IIR protein by affinity cross-linking. However, low levels of TGFβ-IIR were observed in MCF-7 cytosol. Sequencing of the coding region of TGFβ-IIR from MCF-7 cells indicated a point mutation (A439V) in a nonconserved region of the kinase domain. When MCF-7 cells were treated with sublethal doses of Adriamycin that induce cell differentiation, the membrane localization of TGFβ-IIR and TGFβ response were restored. Our results indicate the presence of a prominent, kinase-active TGFβ-IIR in the cytosol of several mammary cell lines. This cytosolic pool of receptors is the only detectable one in MCF-7 cells. Loss of wild-type membrane receptors due to defects in trafficking presents a potential new mechanism for escape from negative growth control.

UR - http://www.scopus.com/inward/record.url?scp=0031018576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031018576&partnerID=8YFLogxK

M3 - Article

C2 - 9041203

AN - SCOPUS:0031018576

VL - 57

SP - 970

EP - 977

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 5

ER -