Page 43 - D. Cancer biology

Cancer-associated protein tetraspanin1 increases cell growth through AMP-
activated protein kinase in atypical endometriosis

Ha-Yeon Shin¹, Doo Byung Chay², Wookyeom Yang¹, Eun-ju Lee¹, Jae-Hoon Kim¹
¹Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea
²Obstertrics and gynecology , Sahmyook medical center, Seoul 02500, Korea
BACKGROUND AIM

Ovarian clear cell carcinoma (OCCC) is an epithelial ovarian In this study, we aimed to discover new mechanisms
cancer, and has poor prognosis due to chemoresistance in its associated with the transformation of endometriosis to
advanced stage. OCCC can arise from endometriosis, a malignant OCCC. We sought to screen for high-risk
common benign disease in women. Atypical endometriosis
(Aty.Em) has been reported to be a precursor to OCCC. endometriosis and identify candidate genes that may serve
However, the molecular mechanism underlying its malignant as targets for preventive treatment, thus blocking the
progression to OCCC has not been fully elucidated. progression of endometriosis to cancerous tumors.
METHODS
RNA sequencing was performed in formalin-fixed,
paraffin-embedded (FFPE) tissues of endometriosis
(n=9), Aty.Em (n=18), adjacent endometriosis to OCCC
(Adj.Em) (n=7), and OCCC (n=17). The differentially Abbreviation
Em ; endometriosis
expressed genes were validated by Aty.Em ; atypical
immunohistochemistry using tissue microarray (TMA). endometriosis
Adj.Em ; adjacent
Cell proliferation and invasion assays of the immortalized endometriosis to OCCC
endometriosis cell lines were conducted via tetraspanin 1 OCCC ; ovarian clear cell
carcinoma
(TSPAN1) overexpression or knockdown.
RESULTS
Figure.1 We identified 14 genes that were increased expression levels in OCCC than the Figure.3 The TSPAN1 increases cell proliferation and clonogenicity in endometriosis cell lines
Em, Aty.Em and Adj.Em group by RNA sequencing analysis.

Figure.4 The TSPAN1 increases cell growth via AMPK in endometriosis cell lines.

Figure2. The TSPAN1 is highly
expressed in human ovarian clear cell
carcinoma cell line and tissue
specimens.
RNA sequencing analysis showed that mRNA expression levels
of TSPAN1 were 2.4-fold higher in Aty.Em and 80.7-fold higher
in clear cell ovarian cancer compared with Aty.Em. In TMA
tissues, expression levels of TSPAN1 were also increased
similarly to mRNA expression levels. We found that TSPAN1
overexpressing endometriosis cell lines grew faster than control
cell lines, and reversed in knockdown of TSPAN1. In
CONCLUSION endometriosis cells, overexpression of TSPAN1 increased AMP-
activated protein kinase (AMPK) activity, and the inhibition of
We confirmed that TSPAN1 increased the growth rate of AMPK activity by siRNA and inhibitor did not increase cell growth
endometriosis cell lines via AMPK activity. These findings by TSPAN1.
suggest the possibility of screening for high-risk
endometriosis, which can progress to clear cell ovarian ACKNOWLEDGEMENTS
cancer, by identifying expression levels of TSPAN1
REFERENCES The study was supported by Basic Science Research program through the National
Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-
2015R1D1A1A01059335, NRF-2017R1D1A1A09000576, and NRF-
Herreros-Villanueva M, Chen CC, Tsai EM, Er TK. Endometriosis-associated 2019R1A6A3A13092928).
ovarian cancer: What have we learned so far? Clinica chimica acta;
international journal of clinical chemistry 2019;493:63-72 doi
10.1016/j.cca.2019.02.016. Contact information Email ; hayeon37@yuhs.ac