Eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 can depend on ER-alpha overexpression in human endometrioid adenocarcinoma

Abstract

Estrogen receptor (ER) and progesterone receptor (PgR) accumulations lead to impairment of gap junctional intercellular communication in endometrial cancer. The task of this study was to explore relationships of Cx26 and Cx43 with anti-apoptotic protein Bcl-xL and proapoptotic agent Bak in ER-alpha and PgR negative or variably positive endometrioid adenocarcinomas. Cx26, Cx43, Bak, Bcl-xL, PgR and ER-alpha were detected in 78 endometrioid adenocarcinomas with immunohistochemistry. There was a remarkable cellular re-distribution of Cx26 and Cx43 from normally membranous location in normal endometrium to aberrantly cytoplasmic expression in endometrioid adenocarcinomas, thus suggesting the decrease of functional membranous gap junctions in the malignancy. Bak failed to correlate with Cx43 regardless of either PgR or ER-alpha status of tumors, while Bcl-xL positively correlated with Cx43 in ER-alpha positive tumors (p = 0.001, r = 0.427) and both PgR positive (p = 0.019, r = 0.312) and negative (p = 0.015, r = 0.509) cancers. Similarly, Bcl-xL significantly associated with Cx26 in ER-alpha positive tumors (p = 0.036, r = 0.267) and both PgR positive (p = 0.026, r = 0.297) and negative (p = 0.046, r = 0.429) cancers. On the contrary, Bak exclusively correlated with Cx26 only in ER-alpha negative tumors (p = 0.027, r = 0.551). ER-alpha status of endometrioid adenocarcinomas could restrict eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 in these tumors.

Chinese abstract

子宫内膜癌中，雌激素受体（ER）和孕激素受体（PR）积累导致细胞间缝隙连接损伤。本研究的任务是探索在ER以及PgR阴性或可逆阳性子宫内膜癌中，含抗凋亡蛋白Bcl-xL和凋亡诱导剂Bak的 Cx26和Cx43之间的关系。 Cx26, Cx43, Bak, Bcl-xL, PgR和ERα在78例子宫内膜癌中采用免疫组织化学的方法进行检测.从正常子宫内膜的细胞膜定位，到子宫内膜癌中反常的胞浆表达，可以观测到Cx26 和 Cx43显著的细胞再分布过程, 表明了恶性肿瘤中的功能性膜缝隙连接的增长。抛开肿瘤中的PgR或 ER-α来看Bak与Cx43并没有关联，而Bcl-xL和Cx43在ER-α阳性(p=0.001, r=0.427)和PgR阳性(p=0.019,r=0.312)以及阴性(p=0.015,r=0.509)的癌症中为正相关。与之相似，在ER-α阳性(p=0.036,r=0.267)和PgR阳性(p=0.026,r=0.297)以及阴性(p=0.046,r=0.429)肿瘤中Bcl-xL与Cx26显著相关。相反地，Bak唯一与Cx26 的相关仅发生在ER-α阴性(p=0.027,r=0.551)的肿瘤中。子宫内膜癌中ER-alpha的状态可以对这些肿瘤中反常表达的Cx43 和Cx26最终的凋亡诱导或抗凋亡冲击加以限制。

• Apoptosis
• connexins
• endometrioid adenocarcinoma
• estrogen and progesterone receptors

Acknowledgements

The authors would like to thank the International Society of Gynecological Endocrinology for ranking of this work among the 100 best winning abstracts in UNDER 34 COMPETITION for 14th World Congress of Gynecological Endocrinology held in Florence. We are very grateful for this outstanding initiative of the Society, which helps young doctors from all over the world to participate in this global meeting with vibrant scientific atmosphere and to challenge many tasks for further development of young researchers.

Declaration of interest

Authors report no conflict of interest.