Minegishi T, Kameda T, Hirakawa T, Abe K, Tano M, Ibuki Y
Department of Obstetrics and Gynecology School of Medicine, Gunma University, Maebashi, Japan.
Clin Cancer Res. 2000 Jul;6(7):2764-70.
Activin receptors (ActRs) and gonadotropin receptor mRNA expression were investigated in 18 human ovarian epithelial neoplasms. Northern blot analysis showed the presence of 3.0-kb type Ia ActR, 6.0- and 3.0-kb type IIa ActR, and 5.0-kb type IIb ActR mRNA transcripts in total RNA prepared from the cancer tissues. One carcinoma showed two major transcripts of a follicle-stimulating hormone receptor (FSH-R) gene, 4.1 and 2.4 kb, whereas the other two carcinomas showed two major transcripts of the luteinizing hormone/human chorionic gonadotropin receptor (LH-R) gene, 5.4 and 2.4 kb. These results were further analyzed by studying the corresponding PCR-amplified FSH and LH-R cDNA obtained by reverse transcription of total RNA. Expression of FSH-R mRNA was confirmed in about half of the cancer tissues. The size of the FSH-R reverse transcription-PCR product was the same as in normal ovarian follicles. Similarly, expression of LH-R mRNA was also detected in about half of the cancers. Normal ovaries and cancer tissues were homogenized, and activin concentrations were measured in extracts. Activin levels in normal ovarian tissue were around 0.59 +/- 0.01 ng/mg protein (mean +/- SE; n = 5), and activin production was detected in every cancer tissue, except one--serous adenocarcinoma. The findings in this study demonstrated that activin and ActRs are present in and synthesized by human ovarian epithelial neoplasms. Thus, activin seems to be available as an autocrine/paracrine factor in epithelial neoplasms and may contribute to the expression of FSH-R, although the roles of activin and gonadotropin in tumorigenesis has yet to be defined.
在18例人类卵巢上皮性肿瘤中研究了激活素受体(ActRs)和促性腺激素受体mRNA的表达。Northern印迹分析显示,从癌组织制备的总RNA中存在3.0 kb的I型a类ActR、6.0 kb和3.0 kb的II型a类ActR以及5.0 kb的II型b类ActR mRNA转录本。1例癌显示卵泡刺激素受体(FSH-R)基因的两种主要转录本,分别为4.1 kb和2.4 kb,而另外2例癌显示促黄体生成素/人绒毛膜促性腺激素受体(LH-R)基因的两种主要转录本,分别为5.4 kb和2.4 kb。通过研究由总RNA逆转录得到的相应PCR扩增的FSH和LH-R cDNA对这些结果进行了进一步分析。约一半的癌组织中证实有FSH-R mRNA表达。FSH-R逆转录-PCR产物的大小与正常卵巢卵泡中的相同。同样,约一半的癌中也检测到LH-R mRNA表达。将正常卵巢和癌组织匀浆,测定提取物中的激活素浓度。正常卵巢组织中的激活素水平约为0.59±0.01 ng/mg蛋白质(平均值±标准误;n = 5),除1例浆液性腺癌外,每个癌组织中均检测到激活素产生。本研究结果表明,激活素和ActRs存在于人类卵巢上皮性肿瘤中并由其合成。因此,激活素似乎可作为上皮性肿瘤中的自分泌/旁分泌因子,可能有助于FSH-R的表达,尽管激活素和促性腺激素在肿瘤发生中的作用尚未明确。