Marselina Irasonia Tan and Yelliantty School of Life Science and Technology, Bandung Institute of Technology Bandung, IndonesiaCorrespondence email: yelliantty@gmail.com

GPR55 is a member of G protein-coupled receptors that could probably bind to several lipid ligands such as lysophosphatidylinositol (LPI). Previous studies showed that GPR55 is expressed in various types of tumors in humans and may increase cancer cell proliferation through the over activation of the kinase signaling cascade. However, expression patterns, physiopathological relevance, and signaling pathways of this protein remain largely unknown in ovarian cancer. The aim of this study was to analyze the expression and function of GPR55 in ovarian cancer cells (SKOV3), which were induced by lysophosphatidylinositol and estradiol. Our data indicated that GPR55 is expressed higher in SKOV3 cells which is induced by LPI compared to control. In addition, proliferation activity of SKOV3 was also regulated by LPI and estradiol. An increment of proliferation activity induced by LPI in SKOV3, which probably bind to GPR55 demonstrated that GPR55 was probably important to stimulate cell proliferation of human ovarian cancer. Key words: GPR55, lysophophatidylinositol, ovarian cancer

Ovarian cancer is the ninth most common cancer in women. It ranks fifth as the cause of cancer death in women.1 Recent study2 showed that GPR55 was expressed in ovarian cancer cell line (SKOV3), but its function is still unknown. GPR55 is a member of G protein-coupled receptors that could probably bind to several lipid ligands such as lysophosphatidylinositol (LPI).3 Previous studies showed that GPR55 is expressed in various types of tumors in humans and may increase cancer cell proliferation through the over activation of the kinase signaling cascade. 4,5

GPR55 PCNA ActinFigure 1. Western blot analysis of GPR55 and PCNA in SKOV3 cells.2.5

2

The aim of this study was to analyze the expression and function of GPR55 in ovarian cancer cells (SKOV3), and its proliferation which were induced by lysophosphatidylinositol and 17-estradiol.

1.5 PCNA 1 GPR55

0.5

0 LPI LPI+17-estradiol 17-estradiol Control

Western Blotting Treatment (72 hr) LPI (1M) LPI (1M)+17Estradiol(1M) 17Estradiol(1M) Serum Free Defined Medium (SFDM) (Control) GPR55 PCNA Actin

Figure 2. Expression of GPR55 and PCNA in SKOV3 cells. Highest level of GPR55 expression was found in SKOV3 cells that were treated by 17-estradiol. GPR55 expression in cells treated by LPI is lower than control. Highest level of PCNA expression was found in cells treated by LPI+17-estradiol. PCNA expression in cells treated by LPI is relative higher than control

SKOV 3

LPI does not significantly affect the expression of GPR55 and proliferation in SKOV 3 cells. However, LPI along with 17-estradiol can increase SKOV3 proliferation.

1. Which is the dominant pathway activated by LPI in ovarian cancer cells(SKOV3), resulting in proliferation or migration? 2. Are there any differences in GPR55 expression in normal ovarian cells than cancer? 3. Are there any differences in the effect of LPI in normal ovarian cells than cancer?

1. 2. 3. 4. 5.

Colombo, N., M. Peiretti, et al. (2010). "Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up." Annals of Oncology 21(suppl 5): v23-v30. Gunarta, I. K. (2010). Effect of 17-Estradiol and Type IV Collagen on GPR55 Gene Expression in SKOV-3 Ovarian Cancer Cell Line. School of Life Science and Technology. Bandung, Bandung Institute of Technology. Undergraduate. Okuno, T. and T. Yokomizo (2011). "What is the natural ligand of GPR55?" Journal of Biochemistry 149(5): 495-497. Pineiro, R., T. Maffucci, et al. (2011). "The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation." Oncogene 30(2): 142-152. Ruth A, R. (2011). "L--Lysophosphatidylinositol meets GPR55: a deadly relationship." Trends in Pharmacological Sciences 32(5): 265-269.