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Loss of expression of tropomyosin-1, a novel class II tumor suppressor that induces anoikis, in primary breast tumors

Oncogene volume 22, pages 6194–6203 (2003)Cite this article

Abstract

Suppression of tropomyosins (TMs), a family of actin-binding, microfilament-associated proteins, is a prominent feature of many transformed cells. Yet it is unclear whether downregulation of TMs occur in human tumors. We have investigated the expression of tropomyosin-1 (TM1) in human breast carcinoma tissues by in situ hybridization and immunofluorescence. TM1 mRNA and protein are readily detectable in normal mammary tissue. In contrast, TM1 expression is abolished in the primary human breast tumors. Expression of other TM isoforms, however, is variable among the tumors. The consistent and profound downregulation of TM1 suggests that TM1 may be a novel and useful biomarker of mammary neoplasms. These data also support the hypothesis that suppression of TM1 expression during the malignant conversion of mammary epithelium as a contributing factor of breast cancer. In support of this hypothesis, we show that the ability to suppress malignant growth properties of breast cancer cells is specific to TM1 isoform. Investigations into the mechanisms of TM1-induced tumor suppression reveal that TM1 induces anoikis (detachment induced apoptosis) in breast cancer cells. Downregulation of TM1 in breast tumors may destabilize microfilament architecture and confer resistance to anoikis, which facilitates survival of neoplastic cells outside the normal microenvironment and promote malignant growth.

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Acknowledgements

This work is supported by grants from the US Department of Defense Breast Cancer Program (DaMD-98-1-8162 and DAMD-991-9395), American Cancer Society (RPG-99-069-01-CSM), NC Biotechnology Center (ARIG 2000-054) and Kulynych Family Funds For Medical Research. We thank Deanna Brown for her help in tissue screening, and Gilda Saluta of the Tumor Bank of Wake Forest University School of Medicine for providing us tissue specimens used in this study. We thank Dr Ethan Lange for his help in statistical analyses, and Dr Vijay Setaluri for the control adeno virus.

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  1. Gira N Raval and Shantaram Bharadwaj: Both authors contributed equally to this work

Authors and Affiliations

  1. Department of General Surgery, Surgical Oncology and Vascular Surgery Services, Wake Forest University School of Medicine, Winston-Salem, 27157, NC, USA

    Gira N Raval, Shantaram Bharadwaj, Edward A Levine, Randolph L Geary & G L Prasad

  2. Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, 27157, NC, USA

    Mark C Willingham & Tim Kute

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  1. Gira N Raval
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Correspondence to G L Prasad.

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Raval, G., Bharadwaj, S., Levine, E. et al. Loss of expression of tropomyosin-1, a novel class II tumor suppressor that induces anoikis, in primary breast tumors. Oncogene 22, 6194–6203 (2003). https://doi.org/10.1038/sj.onc.1206719

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