Novel function of CDK12 in regulation of functional differentiation of mammary epithelial cells
Public support
Provider
Czech Science Foundation
Programme
Standard projects
Call for proposals
SGA0202600001
Main participants
Ústav molekulární genetiky AV ČR, v. v. i.
Contest type
VS - Public tender
Contract ID
26-21568S
Alternative language
Project name in Czech
Novel function of CDK12 in regulation of functional differentiation of mammary epithelial cells
Annotation in Czech
Replication stress-induced DNA damage is a key trigger for functional differentiation of mammary epithelial cells into milk-secreting alveolar cells, a process involving endoreplication-driven polyploidization. Cyclin-dependent kinase 12 (CDK12) regulates transcription of DNA damage repair pathway genes and is frequently mutated in cancer, but its role in normal mammary gland biology is unexplored. Our preliminary data show that Cdk12 heterozygous mice exhibit lactation defects, and CDK12 inhibition in primary mammary epithelial cells and organoids disrupts lactogenic differentiation, reduces polyploidization, and decreases milk protein production. These findings point to a novel, essential function of CDK12 in mammary gland differentiation, which we will examine using our complementary expertise. By identifying CDK12 as a key player in normal mammary function, this work may provide critical insights into lactation failure and the origins of breast cancer linked to CDK12 mutations.
Scientific branches
R&D category
ZV - Basic research
OECD FORD - main branch
10605 - Developmental biology
OECD FORD - secondary branch
10601 - Cell biology
OECD FORD - another secondary branch
—
CEP - equivalent branches <br>(according to the <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">converter</a>)
EA - Morphology and cytology<br>EB - Genetics and molecular biology
Solution timeline
Realization period - beginning
Jan 1, 2026
Realization period - end
Dec 31, 2028
Project status
Z - Beginning multi-year project
Latest support payment
—
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP26-GA0-GA-R
Data delivery date
May 6, 2026
Finance
Total approved costs
11,440 thou. CZK
Public financial support
11,440 thou. CZK
Other public sources
0 thou. CZK
Non public and foreign sources
0 thou. CZK