Balakrishnan, Ashwini
(2013)
Role of the inositol phosphatase INPP4B in the generation of ovarian teratomas.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Teratomas are a unique class of tumors composed of ecto- meso- and endodermal tissues, all foreign to the site of origin. In humans, the most common teratoma is the ovarian teratoma. Not much is known about the molecular and genetic etiologies of these tumors. Female carriers of the Tgkd transgene are highly susceptible to developing teratomas. Ovaries of Tgkd/+ hemizygous female mice exhibit defects in luteinization, with numerous corpora lutea, some of which contain central trapped, fully-grown oocytes. Genetically, Tgkd teratomas originate from mature oocytes that have completed meiosis I, suggesting that Tgkd teratomas originate from these trapped oocytes. The insertion of the Tgkd transgene 3’ of the Inpp4b gene is associated with decreased expression of INPP4B and changes in intracellular PI3 Kinase/AKT signaling in follicular granulosa cells. An increase in granulosa cell proliferation and a decrease in apoptosis is also observed in Tgkd GCs of late stage follicles. Because INPP4B is not expressed in fully-grown wild-type or Tgkd oocytes, these findings suggest that enhanced activation of the PI3K/AKT pathway caused by the decrease in INPP4B in granulosa cells promotes an ovarian environment defective in folliculogenesis and conducive to teratoma formation.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Balakrishnan, Ashwini | asb50@pitt.edu | ASB50 | |
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| ETD Committee: |
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| Date: |
31 January 2013 |
| Date Type: |
Publication |
| Defense Date: |
28 November 2012 |
| Approval Date: |
31 January 2013 |
| Submission Date: |
12 January 2013 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
201 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Cellular and Molecular Pathology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
OVARIAN TERATOMA
PI3-KINASE/AKT
INPP4B
OOCYTE
GRANULOSA CELL
LUTEINIZED UNRUPTURED FOLLICLE |
| Date Deposited: |
31 Jan 2013 14:55 |
| Last Modified: |
19 Dec 2016 14:40 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/17132 |
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