Yoshinaga Keiji, Mimori Koshi, Yamashita Keishi, Utsunomiya Tohru, Inoue Hiroshi, Mori Masaki
Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu 874-0838, Japan.
Int J Oncol. 2003 Jan;22(1):75-80.
Activin A is a member of the transforming growth factor beta (TGF-beta) superfamily and is a strong differentiation factor of embryonic stem (ES) cells. It is unknown whether activin A has any correlation with carcinoma cell differentiation. We investigated the expression of activin-betaA (Act-betaA) which is a subunit of activin A, its receptor type I and IIb (ActRI, ActRIIb) and its inhibitor, inhibin-alpha (Inh-alpha), which is a subunit of inhibin A in esophageal carcinoma by reverse transcription polymerase chain reaction (RT-PCR) method. Act-betaA was overexpressed in carcinoma tissues significantly (p=0.030). On the other hand, Inh-alpha, ActRI and ActRIIb were neither overexpressed, nor suppressed. In immunohistochemistry and in situ hybridization analysis, Act-betaA expression was mainly derived from carcinoma cells. The mRNA expression of Act-betaA was not associated with carcinoma cell differentiation but lymph node metastasis (n0, 1, 2 vs. n3, 4; p=0.013) and clinical stage (I, II, III vs. IV; p=0.026). Moreover, patients with high mRNA expression of Act-betaA had a tendency to show poor prognosis compared to those with low mRNA expression (p=0.064). The finding indicated that activin A expression might not be associated with carcinoma cell differentiation but tumor aggressiveness such as lymph node metastasis in esophageal carcinoma.
激活素A是转化生长因子β（TGF-β）超家族的成员，是胚胎干细胞（ES）的一种强大分化因子。激活素A与癌细胞分化是否存在关联尚不清楚。我们采用逆转录聚合酶链反应（RT-PCR）方法，研究了激活素A的一个亚基激活素-βA（Act-βA）、其I型和IIb型受体（ActRI、ActRIIb）以及其抑制剂抑制素-α（Inh-α，抑制素A的一个亚基）在食管癌中的表达情况。Act-βA在癌组织中显著过表达（p = 0.030）。另一方面，Inh-α、ActRI和ActRIIb既未过表达，也未受到抑制。在免疫组织化学和原位杂交分析中，Act-βA的表达主要来源于癌细胞。Act-βA的mRNA表达与癌细胞分化无关，但与淋巴结转移（n0、1、2与n > 3、4相比；p = 0.013）和临床分期（I、II、III与IV期相比；p = 0.026）有关。此外，与Act-βA mRNA低表达的患者相比，Act-βA mRNA高表达的患者预后往往较差（p = 0.064）。这一发现表明，激活素A的表达可能与癌细胞分化无关，但与食管癌的肿瘤侵袭性如淋巴结转移有关。
