Endocrine Abstracts

Laron syndrome (LS) is a rare autosomal recessive genetic disorder caused by growth hormone receptor (GH-R) gene mutations, leading to congenital insulin-like growth factor-1 (IGF1) deficiency and dwarfism. Epidemiological studies have shown that there are no LS patients that suffer from cancer, which means they are protected from cancer development. While the mechanisms associated with cancer protection in LS are unknown, cancer protection might involve the insulin (INS) and IGF1 signaling pathways. These hormones have been implicated in the etiology of several epithelial neoplasms and have a crucial role in endometrial cancer development.

To investigate the potential cancer protective pathways in LS patients, our laboratory has previously conducted genome wide transcriptome analyses (microarray analysis) using lymphoblastoid cell lines derived from LS patients and healthy controls. The olfactory receptor (OR5H2) gene was among a group of genes shown to be differentially expressed in LS patients. The involvement of the OR5H2 gene in endometrial cancer biology is unknown. Furthermore, most of the differentially expressed genes, including the OR5H2, were not previously linked to IGF1 signaling.

The aim of the project is to evaluate the expression and regulation of the OR5H2 gene in endometrial cancer cells. In addition, we are interested in assessing the potential regulation of OR5H2 expression by IGF1 and insulin. The overall aim of my project is to elucidate the potential role of OR2H5 in endometrial cancer. Two endometrial cancer cell lines will be used in this project as Type II: Uterine serous papillary endometrial carcinoma type 1-derived and uterine serous papillary endometrial carcinoma type 2-derived (USPC-1 and USPC-2). Utilizing these two types of cells will let us examine also the P-53 effect on the regulation of the target gene, for the USPC2 cell line is P-53 mutant, whereas P-53 is wild type in USPC1 cell line.

Evaluation of OR5H5 basal expression levels in preliminary studies using RT-PCR showed differences in basal expression levels between the two endometrial cancer cell lines.