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Hypoxia Inducible Factor-Alpha Promotes Expression of Pro-tumorigenic Semaphorin7A in Mammary Tumor Cells

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Date Issued:
2015
Summary:
It is estimated that one in eight women will be diagnosed with breast cancer. Developing an understanding of the tumor microenvironment is critical for developing treatments for breast cancer patients. It has been well established that hypoxia, or a lack of oxygen, is fundamental in creating a microenvironment that enables metastasis via eliciting angiogenic processes. Poorly differentiated blood vessels can fashion an oxygen-deprived microenvironment that triggers the expression of transcription factor Hypoxia Inducible Factor alpha HIF-1alpha that in turn can up regulate genes mediating a protumor effect. Our laboratory has discovered that mammary tumors express Semaphorin7a SEMA7A, a HIF-1alpha inducible protein. This study’s objective is to delineate the mechanism for hypoxia induction in mammary cells. Cobalt Chloride CoCl2 was used to mimic hypoxia in mammary tumor cell cultures. Flow cytometry was used to determine HIF-1alpha activity in the mammary cells. Benign EpH4 mammary cells expressing low SEMA7A greatly increased its expression after response to hypoxic stimuli as determined by qPCR and SEMA7A-specific ELISA. Pretreatment of EpH4 cells with a HIF-1alpha inhibitor Chemotin blocked induction of SEMA7A. Paradoxically, CoCl2 did not raise expression in the highly metastatic 4T1 cells which experience high levels of SEMA7A. Treatment of 4T1 cells with Chemotin under normoxic conditions inhibit HIF-1alpha activity and decrease SEMA7A levels. Determining the role of SEMA7A in the hypoxia axis could further elucidate novel pathways in breast cancer, suggesting that malignant tumor cells can utilize HIF-1alpha in a hypoxic independent manner.
Title: Hypoxia Inducible Factor-Alpha Promotes Expression of Pro-tumorigenic Semaphorin7A in Mammary Tumor Cells.
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Name(s): Karram, Joseph P.
Garcia-Areas, Ramon A.
Libreros, Stephania
Graduate College
Castro, C.
Keating, Patricia
Iragavarapu-Charyulu, Vijaya
Type of Resource: text
Genre: Poster
Date Created: 2015
Date Issued: 2015
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 1 p.
Language(s): English
Summary: It is estimated that one in eight women will be diagnosed with breast cancer. Developing an understanding of the tumor microenvironment is critical for developing treatments for breast cancer patients. It has been well established that hypoxia, or a lack of oxygen, is fundamental in creating a microenvironment that enables metastasis via eliciting angiogenic processes. Poorly differentiated blood vessels can fashion an oxygen-deprived microenvironment that triggers the expression of transcription factor Hypoxia Inducible Factor alpha HIF-1alpha that in turn can up regulate genes mediating a protumor effect. Our laboratory has discovered that mammary tumors express Semaphorin7a SEMA7A, a HIF-1alpha inducible protein. This study’s objective is to delineate the mechanism for hypoxia induction in mammary cells. Cobalt Chloride CoCl2 was used to mimic hypoxia in mammary tumor cell cultures. Flow cytometry was used to determine HIF-1alpha activity in the mammary cells. Benign EpH4 mammary cells expressing low SEMA7A greatly increased its expression after response to hypoxic stimuli as determined by qPCR and SEMA7A-specific ELISA. Pretreatment of EpH4 cells with a HIF-1alpha inhibitor Chemotin blocked induction of SEMA7A. Paradoxically, CoCl2 did not raise expression in the highly metastatic 4T1 cells which experience high levels of SEMA7A. Treatment of 4T1 cells with Chemotin under normoxic conditions inhibit HIF-1alpha activity and decrease SEMA7A levels. Determining the role of SEMA7A in the hypoxia axis could further elucidate novel pathways in breast cancer, suggesting that malignant tumor cells can utilize HIF-1alpha in a hypoxic independent manner.
Identifier: FA00005887 (IID)
Collection: FAU Student Research Digital Collection
Note(s): The Sixth Annual Graduate Research Day was organized by Florida Atlantic University’s Graduate Student Association. Graduate students from FAU Colleges present abstracts of original research and posters in a competition for monetary prizes, awards, and recognition.
Held by: Florida Atlantic University Libraries
Sublocation: Digital Library
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00005887
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Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.