Scientific Presentations Summer 2009 - Dana-Farber/Harvard ...

The Potential Role of Pituitary Tumor Transforming Gene 1 in
Breast Cancer Development and Progression
Bhaumika Shah
Mentor: Towia Libermann, PhD
Beth Israel Deaconess Medical Center
Breast cancer is the most common cause of cancer in women and the second most
common cause of cancer death in women in the U.S. While Pituitary Tumor-Transforming
Gene 1 (PTTG1) has been recognized as an oncogene in the context of
several types of tumors and a single nucleotide polymorphism in the PTTG1 gene
has been linked to breast cancer development, no further studies into the potential
role of PTTG1 in breast cancer have been pursued. Our preliminary analysis of
genomic data sets link PTTG1 overexpression to recurrence and poor outcome in
breast cancer patients and provide the basis for our innovative study that PTTG1
is a novel breast cancer oncogene that plays an essential role in breast cancer development,
progression and aggressiveness. We analyzed a variety of publicly available
breast cancer microarray datasets for correlation between high expression of PTTG1
and survival. Kaplan Meier curve analysis demonstrated that high PTTG1 expression
strongly correlated with poor survival. The purpose of this study is to determine the
potential role of PTTG1 in breast cancer development and progression as it relates to
poor outcome. The potential biological relevance of the PTTG1 gene in breast cancer
will be assessed by evaluating its mRNA (real time PCR) and protein expression levels
(Western Blot) in breast cancer tissue and cell lines. We will also verify if PTTG1 promotes
breast cancer survival or if the blockage of PTTG1 gene expression can induce
cell death in breast cancer cells through RNA interference. The preliminary results
display that the PTTG1 is upregulated at both mRNA and protein levels in breast
cancer cell lines. For mRNA levels, about 60% of breast cancer tissue samples were
upregulated from the PTTG1. There were high expression levels for both the PTTG1
mRNA and protein levels in the MDA453 cell line. siRNA will be introduced into
these breast cancer cell lines to verify the effect of PTTG1 blockage on breast cancer
proliferation and apoptosis. We anticipate that PTTG1 overexpression is required for
breast cancer progression and metastasis.