TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence

Autor: He Li, Alexander R. Pinto, Lucy Cassar, Craig Nicholls, Jun-Ping Liu, Lihui Wang, Ruping Chen
Rok vydání: 2016
Předmět:
0301 basic medicine
Telomerase
senescence
Activin Receptors
Type II
Bone Morphogenetic Protein 7
Cell
lcsh:Animal biochemistry
Biochemistry
0302 clinical medicine
Drug Discovery
Cellular Senescence
lcsh:Cytology
Neoplasm Proteins
medicine.anatomical_structure
TGFbeta
030220 oncology & carcinogenesis
Actin-Related Protein 2
embryonic structures
MCF-7 Cells
Female
hTERT
Cell aging
Research Article
Biotechnology
Senescence
Breast Neoplasms
Protein Serine-Threonine Kinases
Biology
Bone Morphogenetic Protein Receptors
Type II
telomerase
03 medical and health sciences
medicine
Humans
Telomerase reverse transcriptase
Smad3 Protein
lcsh:QH573-671
lcsh:QP501-801
Cell growth
Receptor
Transforming Growth Factor-beta Type II
Telomere Homeostasis
Cell Biology
telomeres
BMPRII
Telomere
030104 developmental biology
Cancer cell
Cancer research
Receptors
Transforming Growth Factor beta
breast cancer cells
HeLa Cells
Zdroj: Protein & Cell, Vol 8, Iss 1, Pp 39-54 (2016)
Protein & Cell
ISSN: 1674-8018
1674-800X
DOI: 10.1007/s13238-016-0322-1
Popis: Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis. Mutation of the BMPRII receptor, but not TGFbRII, ACTRIIA or ACTRIIB receptor, inhibits BMP7-induced repression of the hTERT gene promoter activity, leading to increased telomerase activity, lengthened telomeres and continued cell proliferation. Expression of hTERT prevents BMP7-induced breast cancer cell senescence and apoptosis. Thus, our data suggest that BMP7 induces breast cancer cell aging by a mechanism involving BMPRII receptor- and Smad3-mediated repression of the hTERT gene. Electronic supplementary material The online version of this article (doi:10.1007/s13238-016-0322-1) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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