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Understanding Glucose Uptake in Breast Cancer Cells
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Understanding Glucose Uptake in Breast Cancer Cells. |
| 개인저자 | Martin, Joshua A. |
| 단체저자명 | The University of Wisconsin - Madison. Cancer Biology. |
| 발행사항 | [S.l.]: The University of Wisconsin - Madison., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 208 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-06B. Dissertation Abstract International |
| ISBN | 9781392714959 |
| 학위논문주기 | Thesis (Ph.D.)--The University of Wisconsin - Madison, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
Advisor: Alexander, Caroline M. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | Considerable evidence suggests that cancer cells rely disproportionately on glucose uptake for growth, creating a therapeutic opportunity for "starving" cancer cells. Our data implicated a cell surface receptor called LDL receptor related protein-5 (LRP5) in glucose uptake in mammary epithelial cells. Thus, this thesis aimed to interrogate the mechanisms underlying the uptake of glucose into normal and transformed mammary epithelial cells. Firstly, we characterized the expression of the principal family of hexose transporters (GLUT) in breast epithelial cells. We confirmed that glucose uptake was key to the survival of breast cancer cells. While GLUT1 has been shown to be a dominant GLUT, crucial for HER2-induced breast tumor initiation, we found considerable residual glucose uptake upon pharmacologic inhibition. In search of potentially redundant GLUTs, we focused on the co-expressed GLUT, GLUT8. Other studies initially pursued GLUT8 as an alternative transporter to the insulin-activated GLUT, GLUT4, but found that it was inessential to mammalian development, and rarely, if ever, present at the cell surface. In silico analysis showed that several GLUTs are transcribed as different mRNA isomers. For GLUT8, we observed three alternatively spliced isomers and found that only two are competent to produce stable proteins, one a relatively minor species. The dominant isomer in cancer cells does not produce a protein, suggesting that cancer cells have little/no GLUT8 function. More interesting, we revealed that the full-length GLUT8 protein is cleaved to produce a C-terminal peptide, and we speculate that this reaction is typical of metabolic sensors. To test this hypothesis, we aim to find partners for the GLUT8 protein, and to identify cell types that show regulated GLUT8 cleavage. Furthermore, we have shown that knockdown of GLUT8 with shRNA, and other shRNA species, induces senescence in breast cancer cells, but have not fully established the molecular basis for this reaction. This will be important to understanding results from any knockdown experiment, and possibly to understanding senescence of breast tumors in vivo. In summary, we have revealed that the GLUT family is likely to have additional roles besides regulated ectopic glucose uptake and suggest a novel role for the enigmatic GLUT8 transporter. |
| 일반주제명 | Cellular biology. Molecular biology. Biology. |
| 언어 | 영어 |
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