Reference SummaryPei XH, Cancer Cell 2009 May 5;15(5):389-401

Title

 CDK inhibitor p18(INK4c) is a downstream target of GATA3 and restrains mammary luminal progenitor cell proliferation and tumorigenesis.

Authors

 Pei XH; Bai F; Smith MD; Usary J; Fan C; Pai SY; Ho IC; Perou CM; Xiong Y

Journal

 Cancer Cell

Volume

 15

Issue

 5

Year

 2009

Pages

 389-401

Abstract

 Mammary epithelia are composed of luminal and myoepithelial/basal cells whose neoplastic transformations lead to distinct types of breast cancers with diverse clinical features. We report that mice deficient for the CDK4/6 inhibitor p18(Ink4c) spontaneously develop ER-positive luminal tumors at a high penetrance. Ink4c deletion stimulates luminal progenitor cell proliferation at pubertal age and maintains an expanded luminal progenitor cell population throughout life. We demonstrate that GATA3 binds to and represses INK4C transcription. In human breast cancers, low INK4C and high GATA3 expressions are simultaneously observed in luminal A type tumors and predict a favorable patient outcome. Hence, p18(INK4C) is a downstream target of GATA3, constrains luminal progenitor cell expansion, and suppresses luminal tumorigenesis in the mammary gland.

Links

 J:148249 – MGI References
19411068 – National Library of Medicine/PubMed

Strain Notes

Strain Note
C.129(B6) Mutant mice on a C57BL/6 "background were backcrossed for seven generations with BALB/c mice" to generate these mice.
C.129(B6)-Cdkn2ctm1Yxi Mutant mice on a C57BL/6 "background were backcrossed for seven generations with BALB/c mice" to generate these mice.
C.129(B6)-Cdkn2ctm1Yxi/+ Mutant mice on a C57BL/6 "background were backcrossed for seven generations with BALB/c mice" to generate these mice.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C.129(B6)-Cdkn2ctm1Yxi Lung tumor Lung

observed
C.129(B6)-Cdkn2ctm1Yxi Mammary gland carcinoma - ductal Mammary gland

6.7
C.129(B6)-Cdkn2ctm1Yxi Mammary gland carcinoma in situ - ductal Mammary gland

observed
C.129(B6)-Cdkn2ctm1Yxi Mammary gland hyperplasia Mammary gland

observed
C.129(B6)-Cdkn2ctm1Yxi Mammary gland lesion Mammary gland

0
C.129(B6)-Cdkn2ctm1Yxi Mammary gland tumor Mammary gland

23 - 88
C.129(B6)-Cdkn2ctm1Yxi/+ Mammary gland tumor Mammary gland

0 - 44
C.129(B6) Mammary gland tumor Mammary gland

0 - 14
C.129(B6)-Cdkn2ctm1Yxi Mammary gland tumor - luminal Mammary gland

observed
C.129(B6)-Cdkn2ctm1Yxi Pancreas tumor Pancreas

observed
C.129(B6)-Cdkn2ctm1Yxi Pituitary gland tumor Pituitary gland

observed
C.129(B6)-Cdkn2ctm1Yxi Testis tumor Testis

observed
C.129(B6)-Cdkn2ctm1Yxi Thyroid gland tumor Thyroid gland

observed
C.129(B6)-Cdkn2ctm1Yxi (Unspecified organ) tumor (Unspecified organ)

observed