Insulin receptor substrate 1 expression enhances the sensitivity of 32D cells to chemotherapy-induced cell death.

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Holly A Porter; Gregory B Carey; Achsah D Keegan (Profiled Authors: Achsah D Keegan; Gregory B Carey)

Center for Vascular and Inflammatory Diseases, Baltimore, MD 21201, USA. hport001@umaryland.edu
Experimental cell research 2012;318(14):1745-58.

PubMed

Abstract

The adapters IRS1 and IRS2 link growth factor receptors to downstream signaling pathways that regulate proliferation and survival. Both suppress factor-withdrawal-induced apoptosis and have been implicated in cancer progression. However, recent studies suggest IRS1 and IRS2 mediate differential functions in cancer pathogenesis. IRS1 promoted breast cancer proliferation, while IRS2 promoted metastasis. The role of IRS1 and IRS2 in controlling cell responses to chemotherapy is unknown. To determine the role of IRS1 and IRS2 in the sensitivity of cells to chemotherapy, we treated 32D cells lacking or expressing IRS proteins with various concentrations of chemotherapeutic agents. We found that expression of IRS1, in contrast to IRS2, enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. When IRS2 was expressed with IRS1, the cells no longer showed enhanced sensitivity. Expression of IRS1 did not alter the expression of pro- and anti-apoptotic proteins; however, 32D-IRS1 cells expressed higher levels of Annexin A2. In 32D-IRS1 cells, IRS1 and Annexin A2 were both located in cytoplasmic and membrane fractions. We also found that IRS1 coprecipitated with Annexin A2, while IRS2 did not. Decreasing Annexin A2 levels reduced 32D-IRS1 cell sensitivity to chemotherapy. These results suggest IRS1 enhances sensitivity to chemotherapy in part through Annexin A2.

5 Originating Grant

1.

CAREY, GREGORY B

Role of Reactive Oxygen Species in B Lymphoma Fate

27 September 2011 - 31 August 2013
NATIONAL CANCER INSTITUTE
2.

Carey, Gregory B

Selective Targeting of MEK and AKt in Lymphoma and Myeloma Apoptosis

30 September 2009 - 29 September 2010
NATIONAL CANCER INSTITUTE
3.

KEEGAN, ACHSAH D.

Molecular Mechanisms of IL-4 and IL-13 Signaling

1 May 1996 - 30 June 2011
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
4.

KEEGAN, ACHSAH D

MOLECULAR MECHANISM OF IL4 SIGNALING

1 May 1996 - 30 April 2001
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
5.

STRICKLAND, DUDLEY K.

Vascular Biology Training Program

1 July 1991 - 31 August 2014
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Scientific Context

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