| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000435983 |
| 005 | | 20200228111839 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781392714959 |
| 035 | |
▼a (MiAaPQ)AAI27667836 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 574 |
| 100 | 1 |
▼a Martin, Joshua A. |
| 245 | 10 |
▼a Understanding Glucose Uptake in Breast Cancer Cells. |
| 260 | |
▼a [S.l.]:
▼b The University of Wisconsin - Madison.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 208 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-06, Section: B. |
| 500 | |
▼a Advisor: Alexander, Caroline M. |
| 502 | 1 |
▼a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 506 | |
▼a This item must not be added to any third party search indexes. |
| 520 | |
▼a 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. |
| 590 | |
▼a School code: 0262. |
| 650 | 4 |
▼a Cellular biology. |
| 650 | 4 |
▼a Molecular biology. |
| 650 | 4 |
▼a Biology. |
| 690 | |
▼a 0379 |
| 690 | |
▼a 0307 |
| 690 | |
▼a 0306 |
| 710 | 20 |
▼a The University of Wisconsin - Madison.
▼b Cancer Biology. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-06B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0262 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15494645
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1816162 |
| 991 | |
▼a E-BOOK |