Impaired turnover of prolactin receptor contributes to transformation of human breast cells

Alexandr Plotnikov, Bentley Varghese, Thai H. Tran, Chengbao Liu, Hallgeir Rui, Serge Y. Fuchs

Research output: Contribution to journalArticle

Abstract

Signaling by polypeptide hormone prolactin (PRL) is mediated by its cognate receptor (PRLr). FRLr is commonly stabilized in human breast cancer due to decreased phosphorylation of residue Ser349, which when phosphorylated recruits the ßTrcp E3 ubiquitin ligase and facilitates PRLr degradation. Here, we show that an impaired PRLr turnover results in an augmented PRL signaling and PRL-induced transcription. Human mammary epithelial cells harboring degradation-resistant PRLr display accelerated proliferation and increased invasive growth. Conversely, a decrease in PRLr levels achieved by either pharmacologic or genetic means in human breast cancer cells dramatically reduced transformation and tumorigenic properties of these cells. Consequences of alteration of PRLr turnover for homeostasis of ammary cells and development of breast cancers, as well as the utility of therapies that target PRLr function in these malignancies, are discussed.

Original languageEnglish (US)
Pages (from-to)3165-3172
Number of pages8
JournalCancer Research
Volume69
Issue number7
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

Fingerprint

Prolactin Receptors
Prolactin
Breast
Breast Neoplasms
Neoplastic Cell Transformation
Ubiquitin-Protein Ligases
Peptide Hormones
Homeostasis
Epithelial Cells
Phosphorylation
Growth
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Plotnikov, A., Varghese, B., Tran, T. H., Liu, C., Rui, H., & Fuchs, S. Y. (2009). Impaired turnover of prolactin receptor contributes to transformation of human breast cells. Cancer Research, 69(7), 3165-3172. https://doi.org/10.1158/0008-5472.CAN-08-4033

Impaired turnover of prolactin receptor contributes to transformation of human breast cells. / Plotnikov, Alexandr; Varghese, Bentley; Tran, Thai H.; Liu, Chengbao; Rui, Hallgeir; Fuchs, Serge Y.

In: Cancer Research, Vol. 69, No. 7, 01.04.2009, p. 3165-3172.

Research output: Contribution to journalArticle

Plotnikov, A, Varghese, B, Tran, TH, Liu, C, Rui, H & Fuchs, SY 2009, 'Impaired turnover of prolactin receptor contributes to transformation of human breast cells', Cancer Research, vol. 69, no. 7, pp. 3165-3172. https://doi.org/10.1158/0008-5472.CAN-08-4033
Plotnikov, Alexandr ; Varghese, Bentley ; Tran, Thai H. ; Liu, Chengbao ; Rui, Hallgeir ; Fuchs, Serge Y. / Impaired turnover of prolactin receptor contributes to transformation of human breast cells. In: Cancer Research. 2009 ; Vol. 69, No. 7. pp. 3165-3172.
@article{885130a6721845bcb6c96e72fb9c1485,
title = "Impaired turnover of prolactin receptor contributes to transformation of human breast cells",
abstract = "Signaling by polypeptide hormone prolactin (PRL) is mediated by its cognate receptor (PRLr). FRLr is commonly stabilized in human breast cancer due to decreased phosphorylation of residue Ser349, which when phosphorylated recruits the {\ss}Trcp E3 ubiquitin ligase and facilitates PRLr degradation. Here, we show that an impaired PRLr turnover results in an augmented PRL signaling and PRL-induced transcription. Human mammary epithelial cells harboring degradation-resistant PRLr display accelerated proliferation and increased invasive growth. Conversely, a decrease in PRLr levels achieved by either pharmacologic or genetic means in human breast cancer cells dramatically reduced transformation and tumorigenic properties of these cells. Consequences of alteration of PRLr turnover for homeostasis of ammary cells and development of breast cancers, as well as the utility of therapies that target PRLr function in these malignancies, are discussed.",
author = "Alexandr Plotnikov and Bentley Varghese and Tran, {Thai H.} and Chengbao Liu and Hallgeir Rui and Fuchs, {Serge Y.}",
year = "2009",
month = "4",
day = "1",
doi = "10.1158/0008-5472.CAN-08-4033",
language = "English (US)",
volume = "69",
pages = "3165--3172",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

TY - JOUR

T1 - Impaired turnover of prolactin receptor contributes to transformation of human breast cells

AU - Plotnikov, Alexandr

AU - Varghese, Bentley

AU - Tran, Thai H.

AU - Liu, Chengbao

AU - Rui, Hallgeir

AU - Fuchs, Serge Y.

PY - 2009/4/1

Y1 - 2009/4/1

N2 - Signaling by polypeptide hormone prolactin (PRL) is mediated by its cognate receptor (PRLr). FRLr is commonly stabilized in human breast cancer due to decreased phosphorylation of residue Ser349, which when phosphorylated recruits the ßTrcp E3 ubiquitin ligase and facilitates PRLr degradation. Here, we show that an impaired PRLr turnover results in an augmented PRL signaling and PRL-induced transcription. Human mammary epithelial cells harboring degradation-resistant PRLr display accelerated proliferation and increased invasive growth. Conversely, a decrease in PRLr levels achieved by either pharmacologic or genetic means in human breast cancer cells dramatically reduced transformation and tumorigenic properties of these cells. Consequences of alteration of PRLr turnover for homeostasis of ammary cells and development of breast cancers, as well as the utility of therapies that target PRLr function in these malignancies, are discussed.

AB - Signaling by polypeptide hormone prolactin (PRL) is mediated by its cognate receptor (PRLr). FRLr is commonly stabilized in human breast cancer due to decreased phosphorylation of residue Ser349, which when phosphorylated recruits the ßTrcp E3 ubiquitin ligase and facilitates PRLr degradation. Here, we show that an impaired PRLr turnover results in an augmented PRL signaling and PRL-induced transcription. Human mammary epithelial cells harboring degradation-resistant PRLr display accelerated proliferation and increased invasive growth. Conversely, a decrease in PRLr levels achieved by either pharmacologic or genetic means in human breast cancer cells dramatically reduced transformation and tumorigenic properties of these cells. Consequences of alteration of PRLr turnover for homeostasis of ammary cells and development of breast cancers, as well as the utility of therapies that target PRLr function in these malignancies, are discussed.

UR - http://www.scopus.com/inward/record.url?scp=66149095511&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66149095511&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-08-4033

DO - 10.1158/0008-5472.CAN-08-4033

M3 - Article

VL - 69

SP - 3165

EP - 3172

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 7

ER -