Decreased levels of the cell-cycle inhibitor p27(Kip1) protein

Prognostic implications in primary breast cancer

Charles Catzavelos, Nandita Bhattacharya, Yee C. Ung, James A. Wilson, Luba Roncari, Charanjit Sandhu, Patricia Shaw, Herman Yeger, Isabella Morava-Protzner, Linda Kapusta, Edmée Franssen, Kathleen I. Pritchard, Joyce M Slingerland

Research output: Contribution to journalArticle

771 Citations (Scopus)

Abstract

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for reliable prognostic markers to assist clinicians in making management decisions. Although a variety of factors have been tested, only tumor stage, grade, size, hormone receptor status, and S-phase fraction are used on a routine basis. The cell cycle is governed by a family of cyclin-dependent kinases (cdks), which are regulated by associated cyclins and by phosphorylation. p27(Kip1), a cyclin-dependent kinase inhibitor, regulates progression from G1 into S phase by binding and inhibiting cyclin/cdks. p27(Kip1) protein levels and/or activity are upregulated by growth inhibitory cytokines including transforming growth factor-β (TGF-β) and, thus, provide an important link between extracellular regulators and the cell cycle. Loss of p27(Kip1), a negative cell-cycle regulator, may contribute to oncogenesis and tumor progression. However, p27(Kip1) mutations in human tumors are extremely rare. We have demonstrated by immunohistochemistry that p27(Kip1) protein levels are reduced in primary breast cancers and that this is associated with tumor progression in both in situ and invasive lesions. This was confirmed by western analysis, reflected in increased G1/S-phase cyclin-dependent kinase activities and shown to be regulated posttranscriptionally by in situ hybridization. Furthermore, on multivariate analysis, low p27(Kip1) is a predictor of reduced disease-free survival. This simple and reliable immunohistochemical assay may become a routine part of breast cancer evaluation and may influence patient management.

Original languageEnglish
Pages (from-to)227-230
Number of pages4
JournalNature Medicine
Volume3
Issue number2
DOIs
StatePublished - Feb 19 1997
Externally publishedYes

Fingerprint

Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases
Tumors
Cell Cycle
Cells
Breast Neoplasms
Cyclins
S Phase
Neoplasms
Phosphorylation
Transforming Growth Factors
G1 Phase
Assays
Disease-Free Survival
In Situ Hybridization
Hormones
Cytokines
Cause of Death
Decision Making
Carcinogenesis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Decreased levels of the cell-cycle inhibitor p27(Kip1) protein : Prognostic implications in primary breast cancer. / Catzavelos, Charles; Bhattacharya, Nandita; Ung, Yee C.; Wilson, James A.; Roncari, Luba; Sandhu, Charanjit; Shaw, Patricia; Yeger, Herman; Morava-Protzner, Isabella; Kapusta, Linda; Franssen, Edmée; Pritchard, Kathleen I.; Slingerland, Joyce M.

In: Nature Medicine, Vol. 3, No. 2, 19.02.1997, p. 227-230.

Research output: Contribution to journalArticle

Catzavelos, C, Bhattacharya, N, Ung, YC, Wilson, JA, Roncari, L, Sandhu, C, Shaw, P, Yeger, H, Morava-Protzner, I, Kapusta, L, Franssen, E, Pritchard, KI & Slingerland, JM 1997, 'Decreased levels of the cell-cycle inhibitor p27(Kip1) protein: Prognostic implications in primary breast cancer', Nature Medicine, vol. 3, no. 2, pp. 227-230. https://doi.org/10.1038/nm0297-227
Catzavelos, Charles ; Bhattacharya, Nandita ; Ung, Yee C. ; Wilson, James A. ; Roncari, Luba ; Sandhu, Charanjit ; Shaw, Patricia ; Yeger, Herman ; Morava-Protzner, Isabella ; Kapusta, Linda ; Franssen, Edmée ; Pritchard, Kathleen I. ; Slingerland, Joyce M. / Decreased levels of the cell-cycle inhibitor p27(Kip1) protein : Prognostic implications in primary breast cancer. In: Nature Medicine. 1997 ; Vol. 3, No. 2. pp. 227-230.
@article{44944ae533d2465e896c886046f5f5a1,
title = "Decreased levels of the cell-cycle inhibitor p27(Kip1) protein: Prognostic implications in primary breast cancer",
abstract = "Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for reliable prognostic markers to assist clinicians in making management decisions. Although a variety of factors have been tested, only tumor stage, grade, size, hormone receptor status, and S-phase fraction are used on a routine basis. The cell cycle is governed by a family of cyclin-dependent kinases (cdks), which are regulated by associated cyclins and by phosphorylation. p27(Kip1), a cyclin-dependent kinase inhibitor, regulates progression from G1 into S phase by binding and inhibiting cyclin/cdks. p27(Kip1) protein levels and/or activity are upregulated by growth inhibitory cytokines including transforming growth factor-β (TGF-β) and, thus, provide an important link between extracellular regulators and the cell cycle. Loss of p27(Kip1), a negative cell-cycle regulator, may contribute to oncogenesis and tumor progression. However, p27(Kip1) mutations in human tumors are extremely rare. We have demonstrated by immunohistochemistry that p27(Kip1) protein levels are reduced in primary breast cancers and that this is associated with tumor progression in both in situ and invasive lesions. This was confirmed by western analysis, reflected in increased G1/S-phase cyclin-dependent kinase activities and shown to be regulated posttranscriptionally by in situ hybridization. Furthermore, on multivariate analysis, low p27(Kip1) is a predictor of reduced disease-free survival. This simple and reliable immunohistochemical assay may become a routine part of breast cancer evaluation and may influence patient management.",
author = "Charles Catzavelos and Nandita Bhattacharya and Ung, {Yee C.} and Wilson, {James A.} and Luba Roncari and Charanjit Sandhu and Patricia Shaw and Herman Yeger and Isabella Morava-Protzner and Linda Kapusta and Edm{\'e}e Franssen and Pritchard, {Kathleen I.} and Slingerland, {Joyce M}",
year = "1997",
month = "2",
day = "19",
doi = "10.1038/nm0297-227",
language = "English",
volume = "3",
pages = "227--230",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Decreased levels of the cell-cycle inhibitor p27(Kip1) protein

T2 - Prognostic implications in primary breast cancer

AU - Catzavelos, Charles

AU - Bhattacharya, Nandita

AU - Ung, Yee C.

AU - Wilson, James A.

AU - Roncari, Luba

AU - Sandhu, Charanjit

AU - Shaw, Patricia

AU - Yeger, Herman

AU - Morava-Protzner, Isabella

AU - Kapusta, Linda

AU - Franssen, Edmée

AU - Pritchard, Kathleen I.

AU - Slingerland, Joyce M

PY - 1997/2/19

Y1 - 1997/2/19

N2 - Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for reliable prognostic markers to assist clinicians in making management decisions. Although a variety of factors have been tested, only tumor stage, grade, size, hormone receptor status, and S-phase fraction are used on a routine basis. The cell cycle is governed by a family of cyclin-dependent kinases (cdks), which are regulated by associated cyclins and by phosphorylation. p27(Kip1), a cyclin-dependent kinase inhibitor, regulates progression from G1 into S phase by binding and inhibiting cyclin/cdks. p27(Kip1) protein levels and/or activity are upregulated by growth inhibitory cytokines including transforming growth factor-β (TGF-β) and, thus, provide an important link between extracellular regulators and the cell cycle. Loss of p27(Kip1), a negative cell-cycle regulator, may contribute to oncogenesis and tumor progression. However, p27(Kip1) mutations in human tumors are extremely rare. We have demonstrated by immunohistochemistry that p27(Kip1) protein levels are reduced in primary breast cancers and that this is associated with tumor progression in both in situ and invasive lesions. This was confirmed by western analysis, reflected in increased G1/S-phase cyclin-dependent kinase activities and shown to be regulated posttranscriptionally by in situ hybridization. Furthermore, on multivariate analysis, low p27(Kip1) is a predictor of reduced disease-free survival. This simple and reliable immunohistochemical assay may become a routine part of breast cancer evaluation and may influence patient management.

AB - Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for reliable prognostic markers to assist clinicians in making management decisions. Although a variety of factors have been tested, only tumor stage, grade, size, hormone receptor status, and S-phase fraction are used on a routine basis. The cell cycle is governed by a family of cyclin-dependent kinases (cdks), which are regulated by associated cyclins and by phosphorylation. p27(Kip1), a cyclin-dependent kinase inhibitor, regulates progression from G1 into S phase by binding and inhibiting cyclin/cdks. p27(Kip1) protein levels and/or activity are upregulated by growth inhibitory cytokines including transforming growth factor-β (TGF-β) and, thus, provide an important link between extracellular regulators and the cell cycle. Loss of p27(Kip1), a negative cell-cycle regulator, may contribute to oncogenesis and tumor progression. However, p27(Kip1) mutations in human tumors are extremely rare. We have demonstrated by immunohistochemistry that p27(Kip1) protein levels are reduced in primary breast cancers and that this is associated with tumor progression in both in situ and invasive lesions. This was confirmed by western analysis, reflected in increased G1/S-phase cyclin-dependent kinase activities and shown to be regulated posttranscriptionally by in situ hybridization. Furthermore, on multivariate analysis, low p27(Kip1) is a predictor of reduced disease-free survival. This simple and reliable immunohistochemical assay may become a routine part of breast cancer evaluation and may influence patient management.

UR - http://www.scopus.com/inward/record.url?scp=16944363001&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=16944363001&partnerID=8YFLogxK

U2 - 10.1038/nm0297-227

DO - 10.1038/nm0297-227

M3 - Article

VL - 3

SP - 227

EP - 230

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 2

ER -