Int6 reduction activates stromal fibroblasts to enhance transforming activity in breast epithelial cells

Cell & Bioscience
Jinfeng SuoEric C Chang

Abstract

The INT6 gene was first discovered as a site of integration in mouse mammary tumors by the mouse mammary tumor virus; however, INT6's role in the development of human breast cancer remains largely unknown. By gene silencing, we have previously shown that repressing INT6 promotes transforming activity in untransformed human mammary epithelial cells. In the present study, guided by microarray data of human tumors, we have discovered a role of Int6 in stromal fibroblasts. We searched microarray databases of human tumors to assess Int6's role in breast cancer. While INT6 expression levels, as expected, were lower in breast tumors than in adjacent normal breast tissue samples, INT6 expression levels were also substantially lower in tumor stroma. By immunohistochemistry, we determined that the low levels of INT6 mRNA observed in the microarray databases most likely occurs in stromal fibroblasts, because far fewer fibroblasts in the tumor tissue showed detectable levels of the Int6 protein. To directly investigate the effects of Int6 repression on fibroblasts, we silenced INT6 expression in immortalized human mammary fibroblasts (HMFs). When these INT6-repressed HMFs were co-cultured with breast cancer cells, the abilities of the latt...Continue Reading

References

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Citations

Jul 19, 2016·Trends in Cell Biology·Jennifer ChuJerry Pelletier
Mar 23, 2017·European Journal of Pharmacology·Annelise CarvalhoVéronique Mathieu
Aug 4, 2021·Nature Reviews. Cancer·Lucilla FabbriStéphan Vagner
Jul 10, 2020·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Yousif A KaririEmad A Rakha

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Methods Mentioned

BETA
ELISA
enzyme-linked immunosorbent assay
fluorescence microscopy
transfection

Software Mentioned

Slidebook
Oncomine
Histoscore

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