The hippo signaling transducer TAZ regulates mammary gland morphogenesis and carcinogen-induced mammary tumorigenesis

Kayla E. Denson, Ashley L. Mussell, He Shen, Alexander Truskinovsky, Nuo Yang, Natesh Parashurama, Yanmin Chen, Costa Frangou, Fajun Yang, Jianmin Zhang

Research output: Contribution to journalArticle

Abstract

Hippo signaling pathway is an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, apoptosis and stem cell self-renewal. TAZ (transcriptional coactivator with the PDZ-binding motif) is a key downstream effector of the mammalian Hippo pathway. Here, using a transgenic mouse model with mammary-gland-specific expression of constitutively active TAZ, we found that TAZ induction in mammary epithelial cells was associated with an increase in mammary glandular size, which probably resulted from adipocyte hypertrophy. Consistent with its known oncogenic potential, we observed tumor formation in TAZ transgenic mice after administration of the carcinogen 7,12-dimethylbenzanthracene (DMBA) and demonstrated that tumorigenesis was reliant on the presence of TAZ. Our findings establish a previously unknown roles of TAZ in regulating both mammary gland morphogenesis as well as carcinogen-induced mammary tumor formation.

Original languageEnglish (US)
Article number6449
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Human Mammary Glands
Transducers
Morphogenesis
Carcinogens
Transgenic Mice
Carcinogenesis
Breast
9,10-Dimethyl-1,2-benzanthracene
Organ Size
Adipocytes
Hypertrophy
Epithelial Cells
Cell Proliferation
Apoptosis
Breast Neoplasms
Neoplasms
Cell Self Renewal

ASJC Scopus subject areas

  • General

Cite this

Denson, K. E., Mussell, A. L., Shen, H., Truskinovsky, A., Yang, N., Parashurama, N., ... Zhang, J. (2018). The hippo signaling transducer TAZ regulates mammary gland morphogenesis and carcinogen-induced mammary tumorigenesis. Scientific Reports, 8(1), [6449]. https://doi.org/10.1038/s41598-018-24712-5

The hippo signaling transducer TAZ regulates mammary gland morphogenesis and carcinogen-induced mammary tumorigenesis. / Denson, Kayla E.; Mussell, Ashley L.; Shen, He; Truskinovsky, Alexander; Yang, Nuo; Parashurama, Natesh; Chen, Yanmin; Frangou, Costa; Yang, Fajun; Zhang, Jianmin.

In: Scientific Reports, Vol. 8, No. 1, 6449, 01.12.2018.

Research output: Contribution to journalArticle

Denson, KE, Mussell, AL, Shen, H, Truskinovsky, A, Yang, N, Parashurama, N, Chen, Y, Frangou, C, Yang, F & Zhang, J 2018, 'The hippo signaling transducer TAZ regulates mammary gland morphogenesis and carcinogen-induced mammary tumorigenesis', Scientific Reports, vol. 8, no. 1, 6449. https://doi.org/10.1038/s41598-018-24712-5
Denson, Kayla E. ; Mussell, Ashley L. ; Shen, He ; Truskinovsky, Alexander ; Yang, Nuo ; Parashurama, Natesh ; Chen, Yanmin ; Frangou, Costa ; Yang, Fajun ; Zhang, Jianmin. / The hippo signaling transducer TAZ regulates mammary gland morphogenesis and carcinogen-induced mammary tumorigenesis. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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