Date of Award

2011

Degree Name

Biological Sciences

College

College of Science

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Eric R Blough

Second Advisor

David S. Mallory

Third Advisor

Bin Wang

Abstract

Cancer cachexia is a muscle wasting condition that occurs in response to a malignant growth in the body. Cachexia is associated with heart failure and is estimated to be the immediate cause of death in about a third of all cancer patients. The purpose of this study was to investigate cardiac atrophy in the APCmin/+ mouse model of colorectal cancer. Compared to age matched C57BL/6 (BL6) mice, APCmin/+ body mass and heart mass were lower at 12 (11.1 Ѡ4.5% and 7.6 Ѡ2.8%, respectively) and 20-weeks (26.1 Ѡ2.5% and 6.0 Ѡ3.8%, respectively) of age (P < 0.05). Immunoblot analysis revealed that these changes in mass were accompanied by increased activation of protein kinase B (Akt Thr 473: 74.4 Ѡ10.9% and 216.0 Ѡ19.6% ; Akt Ser 308: 161.6 Ѡ31.7% and 367.4 Ѡ41.6% at 12- and 20-weeks, respectively, (P < 0.05)), mammalian target of rapamycin (mTOR Ser2448: 23.2 Ѡ13.2% and 44.0 Ѡ16.4% at 12- and 20-weeks, respectively, (P < 0.05)), 5' adenosine monophosphate-activated protein kinase (AMPK: 19.6 Ѡ5.2% and 22.5 Ѡ5.5% at 12- and 20-weeks, respectively, (P < 0.05)) and elevated levels of the autophagy regulator beclin1 (4.7 Ѡ3.3% and 9.5 Ѡ3.0% at 12- and 20-weeks, respectively, (P < 0.05)). No evidence of increased cardiac apoptosis, protein ubiquitination or activation of cardiac caspases or calpains was noted. Taken together, these data suggest that the cardiac atrophy that occurs in the 12- and 20-week old APCmin/+ mouse is relatively modest compared to that seen with other tumor models [1] and is associated with evidence of increased cardiac autophagy.

Subject

Cancer cells

Subject

Cachexia

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