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Spontaneously immortalised bovine mammary epithelial cells exhibit a distinct gene expression pattern from the breast cancer cells.
- Source :
-
BMC cell biology [BMC Cell Biol] 2010 Oct 22; Vol. 11, pp. 82. Date of Electronic Publication: 2010 Oct 22. - Publication Year :
- 2010
-
Abstract
- Background: Spontaneous immortalisation of cultured mammary epithelial cells (MECs) is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs) and the changes in gene expression associated with BME65Cs cells.<br />Results: BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous bTERT (bovine Telomerase Reverse Transcriptase) and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs) cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line). In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16INK4a was downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene c-Myc, along with an undetectable level of breast tumor-related gene Bag-1 and TRPS-1, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, DNMT1 is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of p53 and p16INK4a in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of p53 or p16INK4a.<br />Conclusions: Spontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and exhibit non-malignant transformation. Although this cell line displays altered patterns of gene expression, it is clearly distinct from malignant breast cancer cell line. It showed that co-inhibition of cellular senescence and mitochondrial apoptosis pathways coordinates BME65Cs cells immortalisation. Additionally, mechanisms other than gene mutation are likely to be involved in regulation of cellular functions. This study provides an insight into the relationship between cell senescence and immortalisation. BME65Cs cells will be useful in future studies of cellular senescence and tumorigenesis.
- Subjects :
- Animals
Cattle
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p16 genetics
Cyclin-Dependent Kinase Inhibitor p16 metabolism
Cyclin-Dependent Kinase Inhibitor p21 genetics
Cyclin-Dependent Kinase Inhibitor p21 metabolism
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Down-Regulation
Female
Gene Expression Profiling
Humans
Karyotyping
Mammary Glands, Animal pathology
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-2 metabolism
Proto-Oncogene Proteins c-myc genetics
Proto-Oncogene Proteins c-myc metabolism
Telomere metabolism
Transcription Factors genetics
Transcription Factors metabolism
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
Up-Regulation
bcl-2-Associated X Protein genetics
bcl-2-Associated X Protein metabolism
Breast Neoplasms metabolism
Epithelial Cells metabolism
Mammary Glands, Animal cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2121
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- BMC cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 20969773
- Full Text :
- https://doi.org/10.1186/1471-2121-11-82