Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Role of the inositol phosphatase INPP4B in the generation of ovarian teratomas

Balakrishnan, Ashwini (2013) Role of the inositol phosphatase INPP4B in the generation of ovarian teratomas. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

[img]
Preview
PDF (Balakrishnan_Ashwini_Thesis)
Submitted Version

Download (3MB) | Preview

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.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Balakrishnan, Ashwiniasb50@pitt.eduASB50
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorChaillet, J Richardchaillet@pitt.eduCHAILLET
Committee ChairDEFRANCES, MARIEdefrancesmc@upmc.eduMCD14
Committee MemberWALKER, WILLIAMwalkerw@pitt.eduWALKERW
Committee MemberSurti, Urvashisurtus@mail.magee.edu
Committee MemberO'Keefe, Denise Sokeefeds@upmc.edu
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

Metrics

Monthly Views for the past 3 years

Plum Analytics


Actions (login required)

View Item View Item