Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression

Qian Zhang, Kazuhito Sakamoto, Chengbao Liu, Aleata A. Triplett, Wan Chi Lin, Hallgeir Rui, Kay Uwe Wagner

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cyclin D1 regulates cell proliferation and is a candidate molecular target for breast cancer therapy. This study addresses whether Cyclin D1 is indispensable for ErbB2-associated mammary tumor initiation and progression using a breast cancer model in which this cell-cycle regulator can be genetically ablated prior to or after neoplastic transformation. Deficiency in Cyclin D1 delayed tumor onset but did not prevent the occurrence of mammary cancer in mice overexpressing wild-type ErbB2. The lack of Cyclin D1 was associated with a compensatory upregulation of Cyclin D3, which explains why the targeted downregulation of Cyclin D1 in established mammary tumors had no effect on cancer cell proliferation. Cyclin D1 and D3 are overexpressed in human breast cancer cell lines and primary invasive breast cancers, and Cyclin D3 frequently exceeded the expression of Cyclin D1 in ErbB2-positive cases. The simultaneous inhibition of both cyclins in mammary tumor cells reduced cancer cell proliferation in vitro and decreased the tumor burden in vivo. Collectively, the results of this study suggest that only the combined inhibition of Cyclin D1 and D3 might be a suitable strategy for breast cancer prevention and therapy.

Original languageEnglish (US)
Pages (from-to)7513-7524
Number of pages12
JournalCancer Research
Volume71
Issue number24
DOIs
StatePublished - Dec 15 2011

Fingerprint

Cyclin D3
Cyclin D1
Breast Neoplasms
Cell Proliferation
Neoplasms
Cyclins
Tumor Burden
Cell Cycle
Up-Regulation
Down-Regulation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zhang, Q., Sakamoto, K., Liu, C., Triplett, A. A., Lin, W. C., Rui, H., & Wagner, K. U. (2011). Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression. Cancer Research, 71(24), 7513-7524. https://doi.org/10.1158/0008-5472.CAN-11-1783

Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression. / Zhang, Qian; Sakamoto, Kazuhito; Liu, Chengbao; Triplett, Aleata A.; Lin, Wan Chi; Rui, Hallgeir; Wagner, Kay Uwe.

In: Cancer Research, Vol. 71, No. 24, 15.12.2011, p. 7513-7524.

Research output: Contribution to journalArticle

Zhang, Q, Sakamoto, K, Liu, C, Triplett, AA, Lin, WC, Rui, H & Wagner, KU 2011, 'Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression', Cancer Research, vol. 71, no. 24, pp. 7513-7524. https://doi.org/10.1158/0008-5472.CAN-11-1783
Zhang, Qian ; Sakamoto, Kazuhito ; Liu, Chengbao ; Triplett, Aleata A. ; Lin, Wan Chi ; Rui, Hallgeir ; Wagner, Kay Uwe. / Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression. In: Cancer Research. 2011 ; Vol. 71, No. 24. pp. 7513-7524.
@article{f83c82573bbf419380a0bc6806af581a,
title = "Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression",
abstract = "Cyclin D1 regulates cell proliferation and is a candidate molecular target for breast cancer therapy. This study addresses whether Cyclin D1 is indispensable for ErbB2-associated mammary tumor initiation and progression using a breast cancer model in which this cell-cycle regulator can be genetically ablated prior to or after neoplastic transformation. Deficiency in Cyclin D1 delayed tumor onset but did not prevent the occurrence of mammary cancer in mice overexpressing wild-type ErbB2. The lack of Cyclin D1 was associated with a compensatory upregulation of Cyclin D3, which explains why the targeted downregulation of Cyclin D1 in established mammary tumors had no effect on cancer cell proliferation. Cyclin D1 and D3 are overexpressed in human breast cancer cell lines and primary invasive breast cancers, and Cyclin D3 frequently exceeded the expression of Cyclin D1 in ErbB2-positive cases. The simultaneous inhibition of both cyclins in mammary tumor cells reduced cancer cell proliferation in vitro and decreased the tumor burden in vivo. Collectively, the results of this study suggest that only the combined inhibition of Cyclin D1 and D3 might be a suitable strategy for breast cancer prevention and therapy.",
author = "Qian Zhang and Kazuhito Sakamoto and Chengbao Liu and Triplett, {Aleata A.} and Lin, {Wan Chi} and Hallgeir Rui and Wagner, {Kay Uwe}",
year = "2011",
month = "12",
day = "15",
doi = "10.1158/0008-5472.CAN-11-1783",
language = "English (US)",
volume = "71",
pages = "7513--7524",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "24",

}

TY - JOUR

T1 - Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression

AU - Zhang, Qian

AU - Sakamoto, Kazuhito

AU - Liu, Chengbao

AU - Triplett, Aleata A.

AU - Lin, Wan Chi

AU - Rui, Hallgeir

AU - Wagner, Kay Uwe

PY - 2011/12/15

Y1 - 2011/12/15

N2 - Cyclin D1 regulates cell proliferation and is a candidate molecular target for breast cancer therapy. This study addresses whether Cyclin D1 is indispensable for ErbB2-associated mammary tumor initiation and progression using a breast cancer model in which this cell-cycle regulator can be genetically ablated prior to or after neoplastic transformation. Deficiency in Cyclin D1 delayed tumor onset but did not prevent the occurrence of mammary cancer in mice overexpressing wild-type ErbB2. The lack of Cyclin D1 was associated with a compensatory upregulation of Cyclin D3, which explains why the targeted downregulation of Cyclin D1 in established mammary tumors had no effect on cancer cell proliferation. Cyclin D1 and D3 are overexpressed in human breast cancer cell lines and primary invasive breast cancers, and Cyclin D3 frequently exceeded the expression of Cyclin D1 in ErbB2-positive cases. The simultaneous inhibition of both cyclins in mammary tumor cells reduced cancer cell proliferation in vitro and decreased the tumor burden in vivo. Collectively, the results of this study suggest that only the combined inhibition of Cyclin D1 and D3 might be a suitable strategy for breast cancer prevention and therapy.

AB - Cyclin D1 regulates cell proliferation and is a candidate molecular target for breast cancer therapy. This study addresses whether Cyclin D1 is indispensable for ErbB2-associated mammary tumor initiation and progression using a breast cancer model in which this cell-cycle regulator can be genetically ablated prior to or after neoplastic transformation. Deficiency in Cyclin D1 delayed tumor onset but did not prevent the occurrence of mammary cancer in mice overexpressing wild-type ErbB2. The lack of Cyclin D1 was associated with a compensatory upregulation of Cyclin D3, which explains why the targeted downregulation of Cyclin D1 in established mammary tumors had no effect on cancer cell proliferation. Cyclin D1 and D3 are overexpressed in human breast cancer cell lines and primary invasive breast cancers, and Cyclin D3 frequently exceeded the expression of Cyclin D1 in ErbB2-positive cases. The simultaneous inhibition of both cyclins in mammary tumor cells reduced cancer cell proliferation in vitro and decreased the tumor burden in vivo. Collectively, the results of this study suggest that only the combined inhibition of Cyclin D1 and D3 might be a suitable strategy for breast cancer prevention and therapy.

UR - http://www.scopus.com/inward/record.url?scp=84255170423&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84255170423&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-11-1783

DO - 10.1158/0008-5472.CAN-11-1783

M3 - Article

C2 - 22037875

AN - SCOPUS:84255170423

VL - 71

SP - 7513

EP - 7524

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 24

ER -