Down-regulation of T1A12/mac25, a novel insulin-like growth factor binding protein related gene, is associated with disease progression in breast carcinomas (original) (raw)

Oncogene volume 16, pages 2459–2467 (1998)Cite this article

Abstract

To define genes that are essential to the initiation and progression of breast cancer we utilized subtractive hybridization and differential display cloning techniques and isolated over 950 cDNAs from breast cell-lines derived from matched normal and tumor tissue. Of these, 102 cDNAs were characterized by DNA sequencing and Northern blot analysis. GenBank searches showed that one of these genes, T1A12 is identical to mac25, an insulin-like growth factor-binding protein related gene. Antibodies generated against the C-terminal region of the T1A12/mac25 protein were used to investigate its expression in 60 primary breast tissues. Sections of 12 benign, 16 ductal carcinoma in situ and 32 infiltrating ductal carcinoma specimens were examined. Strong immunoperoxidase staining was observed in luminal epithelial cells of normal lobules and ducts, in apocrine cells of cysts and fibroadenomas. Moderate to weak protein expression was found in hyperplastic and DCIS cells, but no specific staining was detected in invasive carcinoma cells. FISH mapping using a PAC clone localized the T1A12/mac25 gene to 4q12-13. Microsatellite length polymorphism was studied using markers for 4q in paired normal and tumor breast tissues. Thirty-three per cent (10/30) of the samples were found to be polymorphic with D4S189 and D4S231 microsatellite markers and LOH was detected in 50% (5/10) of these informative samples. Our data indicate that T1A12/mac25 expression is abrogated during breast cancer progression concomitant with loss of heterozygosity on chromosome 4q. T1A12/mac25 may therefore have a tumor suppressor-like function and its expression could indicate a disease with a more favorable status, having a better prognosis.

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Authors and Affiliations

  1. Tumor Biology Center at the University of Freiburg, Freiburg, 79106, FRG
    Angelika M Burger
  2. Center for Molecular and Structural Biology, Medical University of South Carolina, Charleston, 29425-2213, South Carolina, USA
    X Zhang, Hua Li & Takis Papas
  3. Department of Pathology, Leeds General Infirmary, Leeds, LS2 9JT, UK
    Julian L Ostrowski
  4. Princess Margaret Hospital, Toronto, Canada
    Barbara Beatty
  5. Cancer Therapy and Prevention Research Association, Rome, Italy
    Marco Venanzoni
  6. Department of Laboratory Medicine and Pathobiology, MRC Group in Periodontal Physiology and Women's College Hospital, University of Toronto, Toronto, M5S 1B2, ON, Canada
    Arun Seth

Authors

  1. Angelika M Burger
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  2. X Zhang
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  3. Hua Li
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  4. Julian L Ostrowski
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  5. Barbara Beatty
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  6. Marco Venanzoni
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  7. Takis Papas
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  8. Arun Seth
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Burger, A., Zhang, X., Li, H. et al. Down-regulation of T1A12/mac25, a novel insulin-like growth factor binding protein related gene, is associated with disease progression in breast carcinomas.Oncogene 16, 2459–2467 (1998). https://doi.org/10.1038/sj.onc.1201772

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