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Volume 10 Supplement 2

Breast Cancer Research 2008

Brk expression may affect the differentiation status of breast cancer cells

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The breast tumour kinase Brk (PTK6) is found in over two-thirds of breast cancer cell lines and tumours but is not expressed in normal mammary cells. Brk has previously been shown to play a role in regulating proliferation in breast tumour cells [1]. However, in vivo, the site of Brk expression in normal tissues is restricted to nonproliferating cells that are undergoing terminal differentiation such as those in the gut or the skin [2, 3]. This led us to hypothesise that Brk expression in breast tumours could be reflective of a differentiation phenotype, especially as a previous study had shown that involucrin, a marker of terminal keratinocyte differentiation, was expressed in a subset of tumours [4]. We therefore examined involucrin expression in breast tumour cells lines and patient biopsy samples. In addition we investigated whether inducers of differentiation in keratinocytes such as prolonged culture in suspension or vitamin D3 treatment could also affect differentiation of breast tumour cells.

We found that the expression of Brk in cultured cell lines correlated with involucrin expression. In addition the change in Brk expression, as a result of culture conditions, was accompanied by a change in involucrin levels. Moreover, treatment with vitamin D3 resulted in a decrease in cell numbers in the Brk-positive cell lines relative to the control treatments. The Brk-negative cell line was unaffected by vitamin D3 treatment.

These data suggest that Brk and involucrin may be coregulated and that inducers of differentiation such as vitamin D3 could be considered potential therapeutic strategies.

References

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    Harvey AJ, Crompton MR: Use of RNA interference to validate Brk as a novel therapeutic target in breast cancer: Brk promotes breast carcinoma cell proliferation. Oncogene. 2003, 22: 5006-5010. 10.1038/sj.onc.1206577.

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    Vasioukhin V, Serfas MS, Siyanova EY, Polonskaia M, Costigan VJ, Liu B, Thomason A, Tyner AL: A novel intracellular epithelial cell tyrosine kinase is expressed in the skin and gastrointestinal tract. Oncogene. 1995, 10: 349-357.

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    Llor X, Serfas MS, Bie W, Vasioukhin V, Polonskaia M, Derry J, Abbott CM, Tyner AL: BRK/Sik expression in the gastrointestinal tract and in colon tumors. Clin Cancer Res. 1999, 5: 1767-1777.

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    Tsuda H, Sakamaki C, Fukutomi T, Hirohashi S: Squamoid features and expression of involucrin in primary breast carcinoma associated with high histological grade, tumour cell necrosis and recurrence sites. Br J Cancer. 1997, 75: 1519-1524.

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Acknowledgements

Funded by Breast Cancer Campaign and Brunel University.

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Keywords

  • Breast Cancer Cell
  • Breast Tumour
  • Breast Cancer Cell Line
  • Terminal Differentiation
  • Breast Tumour Cell