Research article summary (published 13 Oct 2009):

TOB suppresses breast cancer tumorigenesis.

Full Abstract

Transducer of ErbB-2 (TOB) is a member of the TOB/Btg gene family. A role for TOB in the suppression of human tumorigenesis has been proposed, based on the observations that TOB-knockout mice spontaneously form tumors and TOB expression is lost in human lung and thyroid cancers. However, the role of TOB in human breast cancer remains unknown. To evaluate the this role, we screened a panel of breast cancer cell lines for TOB expression levels and found that they are inversely correlated with the tumorigenicity and metastatic potential of the cell lines. In addition, we demonstrated for the first time that TOB expression is inversely correlated with breast cancer progression in clinical specimens. These results strongly indicate that the loss of TOB expression plays a role in breast cancer progression. We have also provided the first evidence that TOB functions as a tumor suppressor in breast cancer MCF-7 cells, using gain-of-function and loss-of-function approaches to manipulate TOB expression. Cell-cycle analysis further revealed that TOB can prolong the G1-S phase transition by inducing arrest at G1-S phase. Moreover, upregulation of the cyclin-dependent kinase inhibitor p27 and downregulation of the antiapoptotic proteins Bcl-2 and Bcl-XL were observed in MCF7/TOB transfectants. Conversely, opposite results were observed in shRNA-TOB transfectants. Furthermore, decreased activity of Erk2, AKT, CrkL, PDK1, and Smads were observed in TOB-overexpressing cells. Taken together, these data provide evidence that TOB can function as a tumor suppressor in breast cancer through modulation and regulation of multiple signaling pathways.

Author information

Author/s: O'Malley, Sean (S); Su, Hua (H); Zhang, Tao (T); Ng, Crystal (C); Ge, Hong (H); Tang, Careen K (CK);

Affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, NW, Washington, DC, USA.

Grants: R01CA88871 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Oct; vol 125 (issue 8) : pp 1805-13

Dates: Created 2009/08/26; Completed 2009/09/21;

PMID: 19569230, status: MEDLINE (last retrieval date: 9/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Apoptosis Blotting, Northern Blotting, Western Breast Neoplasms - metabolism; pathology; prevention & control Cell Adhesion Cell Cycle - physiology Cell Line, Tumor Cell Proliferation Enzyme-Linked Immunosorbent Assay Female Fluorescent Antibody Technique Genes, Tumor Suppressor - physiology

Genes, Tumor Suppressor - physiology Humans Immunoblotting Immunoenzyme Techniques Immunoprecipitation Intracellular Signaling Peptides and Proteins - physiology Mice Mice, Nude RNA, Messenger - genetics; metabolism RNA, Small Interfering - pharmacology Reverse Transcriptase Polymerase Chain Reaction Transfection Tumor Suppressor Proteins - physiology

Associated Chemicals: Intracellular Signaling Peptides and Proteins (0) ; RNA, Messenger (0) ; RNA, Small Interfering (0) ; TOB1 protein, human (0) ; Tumor Suppressor Proteins (0)

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