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Frequent loss of Dab2 protein and infrequent promoter hypermethylation in breast cancer

Bagadi, Sarangadhara Appala Raju, Prasad, Chandra Prakash, Srivastava, Anurag, Prashad, Rajinder, Gupta, Siddarth Datta, Ralhan, Ranju·2007·Breast Cancer Research and Treatment
DOI 10.1007/s10549-006-9422-6
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Abstract

Disabled-2 (Dab2), a putative tumor suppressor protein, is lost in 80-90% ovarian tumors and ovarian/breast cancer cell lines. The clinical significance of Dab2 protein in breast cancer remains yet unknown. Immunohistochemical analysis of Dab2 protein showed no detectable expression in 67/91 (74%) breast tumors, while all 10 normal tissues showed presence of Dab2 protein. We hypothesized that epigenetic silencing of Dab2 may account for loss of protein in breast cancer. Methylation of Dab2 exon 1, a putative promoter, was analyzed in six breast cancer cell lines and in 54 primary breast tumors by methylation specific PCR. Methylation was observed in MDA-MB-231 and MDA-MB-157 cells and in 6 of 54 (11%) primary breast tumors that also showed loss of Dab2 protein. Expression of Dab2 transcripts was detected in all cell lines except MDA-MB-157. However, none of these six cell lines showed detectable levels of Dab2 protein by western blotting, while non-malignant mammary epithelial cell line MCF 10A showed Dab2 protein expression. To our knowledge this is the first report showing low frequency of Dab2 (putative) promoter methylation (11%) in primary breast tumors. Frequent loss of Dab2 protein (74%) suggest that hypermethylation of Dab2 promoter may only be one of the mechanisms accounting for its loss in breast cancer. Further, in silico analysis of Dab2 3'-UTR revealed existence of miRNA complimentary to this region of the gene, suggesting microRNA mediated targeting of Dab2 mRN…

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  • Several subsequent reports corroborated loss or reduced Dab2 expression in human breast cancer.

    “Several subsequent reports corroborated loss or a reduced Dab2 expression in human breast cancer (Sheng et al., 2000b; Bagadi et al., 2007).”

    From Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice (2016) · cites this paper as Bagadi et al., 2007

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Metadata

Authors
Bagadi, S. A. R., Prasad, C. P., Srivastava, A., Prashad, R., Gupta, S. D., & Ralhan, R.
Venue
Breast Cancer Research and Treatment
Publisher
Springer Science and Business Media LLC
Published
2006-11-18
Volume
104
Issue
3
Pages
277-286
ISSN
  • 0167-6806
  • 1573-7217
DOI
10.1007/s10549-006-9422-6
Cited by
40
References
1
Language
en
Licence
www.springer.com/tdm (tdm)

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