Title

PTH Type I Receptor Regulatory Proteins and PTHrP in Breast Cancer

Defense Date

7-21-2009

Graduation Date

Fall 1-1-2009

Availability

Campus Only

Submission Type

thesis

Degree Name

MS

Department

Biological Sciences

School

Bayer School of Natural and Environmental Sciences

Committee Chair

W. Bruce Sneddon

Committee Member

Jana Patton-Vogt

Committee Member

Kyle Selcer

Keywords

NHERF1, PTHrP, PTH1R

Abstract

This study investigated the Parathyroid Hormone Type 1 Receptor (PTH1R) and its regulation by the Na+/H+ Exchanger Regulatory Factor 1 (NHERF1). Our data show that when the PTH1R is stimulated by Parathyroid Hormone Related Peptide (PTHrP), the PTH1R initiates a downstream signaling cascade which leads to ERK phosphorylation, a pathway which can lead to cell division and may contribute to breast cancer. Proteins such as NHERF1, which interact with the PTH1R, regulate this pathway. Our data show that NHERF1 lowers PTHrP stimulated phosphorylation of ERK. Our data also demonstrate that knock down of NHERF1 leads to faster invasion by MCF7 cells. Conversely, transfecting NHERF1 into cells such as MDA-MB231 which express low levels of NHERF1 lowers invasive properties in these cells. Taken together, the data support the hypothesis that NHERF1 is a tumor suppressor by inhibiting PTHrP activation of the PTH1R.

Format

PDF

Language

English

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