Abstract 1839: TGFBR1*6A mouse model mimics human breast cancer development and progression

Abstract Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification in human cells depends on the gut microbiome because the microbiome product queuine is required for its installation by the enzyme queuine tRNA ribosyltransferase catalytic subunit 1 (QTRT1) encoded in the human genome. Although tRNA Q-modification has been studied a long time regarding its properties in decoding and tRNA fragment generation, how QTRT1 affects tumorigenesis is still poorly understood. Results: We generated single clones of QTRT1-knockout breast cancer MCF7 cells using Double Nickase Plasmid. The impacts of QTRT1-delection on cell proliferation and migration in vitro were evaluated using cell culture, while the regulations on tumor growth in vivo were evaluated using xenograft BALB/c nude mouse model. We found that QTRT1 completely deleted from human breast cancer MCF7 cells could change the functions of regulation genes which are critical in cell proliferation, tight junction formation, and migration in human breast cancer cells in vitro and a breast tumor mouse model in vivo . We also found that microbiome maybe involved in the breast cancer development in vivo. Conclusions: Our results demonstrate that the QTRT1 gene and microbiome play a critical role in breast cancer development.

Download Full-text

MRCKα Is Dispensable for Breast Cancer Development in the MMTV-PyMT Model

Cells ◽

10.3390/cells10040942 ◽

2021 ◽

Vol 10 (4) ◽

pp. 942

Author(s):

Mei Qi Kwa ◽

Rafael Brandao ◽

Trong H. Phung ◽

Jianfeng Ge ◽

Giuseppe Scieri ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression Signature ◽

Genomic Analysis ◽

Cancer Development ◽

Breast Cancer Cell Lines ◽

Normal Mammary Gland ◽

Breast Cancers ◽

Human Breast ◽

Breast Cancer Development

MRCKα is a ubiquitously expressed serine/threonine kinase involved in cell contraction and F-actin turnover, which is highly amplified in human breast cancer and part of a gene expression signature for bad prognosis. Nothing is known about the in vivo function of MRCKα. To explore MRCKα function in development and in breast cancer, we generated mice lacking a functional MRCKα gene. Mice were born close to the Mendelian ratio and showed no obvious phenotype including a normal mammary gland formation. Assessing breast cancer development using the transgenic MMTV-PyMT mouse model, loss of MRCKα did not affect tumor onset, tumor growth and metastasis formation. Deleting MRCKα and its related family member MRCKβ in two triple-negative breast cancer cell lines resulted in reduced invasion of MDA-MB-231 cells, but did not affect migration of 4T1 cells. Further genomic analysis of human breast cancers revealed that MRCKα is frequently co-amplified with the oncogenes ARID4B and AKT3 which might contribute to the prognostic value of MRCKα expression. Collectively, these data suggest that MRCKα might be a prognostic marker for breast cancer, but probably of limited functional importance.

Download Full-text