gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

c-kit: identification of co-regulated genes in breast cancer patients by gene expression analysis and discrimination of two breast cancer subtypes with stem-cell-like features

Meeting Abstract

  • corresponding author presenting/speaker Achim Rody - Uniklinik Gynäkolgie, Frankfurt, Deutschland
  • Uwe Holtrich - Uniklinik Gynäkolgie, Frankfurt
  • Eugen Ruckhäberle - Uniklinik Gynäkolgie, Frankfurt
  • Regine Gätje - Uniklinik Gynäkolgie, Frankfurt
  • Marc Munnes - Bayer Healthcare AG, Leverkusen
  • Mathias Gehrmann - Bayer Healthcare AG, Leverkusen
  • Katharina Kourtis - Uniklinik Gynäkolgie, Frankfurt
  • Raihana Diallo - Uniklinik Pathologie, Düsseldorf
  • Knut Engels - Uniklinik Pathologie, Frankfurt
  • Gunter von Minckwitz - Uniklinik Gynäkolgie, Frankfurt
  • Thomas Karn - Uniklinik Gynäkolgie, Frankfurt
  • Manfred Kaufmann - Uniklinik Gynäkolgie, Frankfurt

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO081

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Veröffentlicht: 20. März 2006

© 2006 Rody et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.



Expression of the proto-oncogene c-kit, a marker which characterizes the hematopoietic stem cell, has been found in malignant tissue including a subset of breast cancers. c-Kit is also expressed in normal breast tissue and several authors found a loss of c-kit expression in breast carcinoma suggesting it might be involved in the growth control of mammary epithelium. Until now, only a few markers were described to be co-regulated with c-kit as e.g. CK-5/-17, Her-1 and PDGFR. To elucidate the possible role of c-kit in malignant transformation, we analyzed gene expression data of breast cancer patients.

Experimental procedures: Tumor tissue of n=171 breast cancer patients were analyzed by gene expression profiling using Affymetrix Hg U133 Arrays (22,500 genes) and bioinformatic analyses. Tumor samples with high stromal and low epithelial cell content by gene expression profiling were excluded for further analysis.

Summary: A total of 10.5 % of the tumors showed strong c-kit expression (2.5 fold above median). Simple comparison of gene expression profiles of 10 samples with highest c-kit vs. those 10 with lowest expression did not reveal genes with a good correlation to c-kit. However, when samples were first subdivided into molecular tumor subtypes using the intrinsic gene set according to Sorlie et al., and different tumor subtypes were analyzed separately, a strong correlation of c-kit expression with a large cluster of genes containing several for whom c-kit coexpression was already described (HER1, CK-5/-17, PDGFR) as well as several members of the wnt signalling pathway could be revealed, providing a possible novel link to mammary epithelial differentiation and a putative role in characterizing mammary stem cells. Furthermore we could observe within this cluster two distinct subgroups characterized by different ER-expression and high or low proliferation rate.

Conclusions: Gene expression analysis of mammary tumor subgroups according to Sorlie et al. provides new insight in the biological function of c-kit. In combination with wnt-associated genes and differences in ER-expression and high or low proliferation rate, two subgroups with stem-cell-like features can be distinguished, suggesting the existence of a two-stem-cell-hypothesis according to Dontu et al., (Endocrinol Metab, 15(5):193-7, 2004).