Inhibin .ALPHA., .BETA.A Subunit and Activin Type II Receptor mRNAs Are Expressed in Human Brain Tumors.

Abstract

Abstract. Inhibin and activin were initially isolated as regulators of pituitary or gonadal hormone and are now known to be growth factors belonging to the TGF-/3 family with diverse influences on the differentiation and proliferation of various tissues. To investigate the role of inhibin and activin in human brain tumors, the expression of inhibin a, and /3A mRNA as well as activin type II receptor (ACTR II) mRNA were studied in various human brain tumors. The tumors were divided into the following 4 groups: 3 Rathke's cleft cysts and 2 craniopharyngiomas (group 1), 8 meningiomas (group 2), 8 malignant gliomas (group 3), and various other tumors including 1 each of germinoma, astrocytoma, hemangioblastoma, and osteochondroma as well as 2 malignant lymphomas and 2 metastatic squamous cell carcinomas (group 4). Immediately after resection, tumor tissues were homogenized in guanidine thyiocyanate to extract total RNA. PCR was then performed with reverse-transcribed cDNA and the respective amplification primers. DNA bands were obtained by agarose gel electrophoresis. Messenger RNA for the inhibin LA subunit was demonstrated in all of the tissues studied. In contrast, inhibin a subunit mRNA was expressed in 60%, 50%, 75%, and 75% of the tumors in groups 1, 2, 3 and 4, respectively, whereas ACTR II mRNA was demonstrated in 20%, 37.5%, 62.5% and 50% of the tumors in each group. Coexpression of mRNAs for the inhibin a, and 13A subunits and ACTR II occurred in some brain tumors. The levels of inhibin a and ACTR II mRNA tended to be higher in the tumors with a higher grade of malignancy. These results indicate that some human brain tumors express receptors for activin, and that inhibin and activin may play an autocrine or paracrine role in brain tumor tissue.

Inhibin .ALPHA. and .BETA.A Subunit Messenger Ribonucleic Acids Expression in Human Pituitary Adenomas: Studies by Quantitative Reverse Transcription-Polymerase Chain Reaction.

“…Haddad et al [7] concluded that the human gonadotroph adenomas expressed NB mRNA together with a mRNA, but none of them expressed F3A mRNA. As most non-functioning adenomas could be gonadotroph adenomas [13][14][15], the NA mRNA presence in non-functioning adenomas in the present study was not in accord with them. The F'B subunit presence and its level in the normal human pituitary and various pituitary adenomas must await further studies.…”

Regulation of Cell Proliferation, Apoptosis, and Carcinogenesis by Activin

“…Either BMP type I receptor or type II receptor can individually interact with BMP (47). Activin receptor expression has been detected in cell lines from various tissues, including prostate cancer (6)(7)(8), breast cancer (9), keratinocytes (48), erythroleukemia (49), osteoblasts (50), and teratocarcinoma (51), as well as in in vivo human prostate (52), ovary (53), brain tumor (54), oocyte (20), placenta (55,56), and pancreatic cancer (37). Besides binding to activin, both ActR-II and ActR-IIB have shown to bind BMP in the presence of a BMP type I receptor (58,59).…”

Demonstration of Activin in Normal Pituitary and in Various Human Pituitary Adenomas by Immunohistochemistry.

“…So far, Alexander and Klibanski detected inhibin a subunit mRNA in human gonadotropinoma [7] and Haddard et al reported the presence of f3, but not I A subunit mRNA, in gonadotropinomas [8]. On the other hand, we recently found that inhibin a and NA subunits and activin type 2 receptor mRNAs were expressed, with the ubiquitous presence of NA subunit mRNA in all human pituitary adenoma tissues, regardless of their hormone production [9]. This prompted us to investigate the presence of inhibin or activin in various kinds of human pituitary adenoma tissues immunohistochemically with antisera to activin and inhibin a subunit, respectively.…”

“…The modifying role of activin on GH and PRL secretion from human GH adenomas [4,5], and gonadotropinomas [3], and its modifying effect on PRL and ACTH secretion in rat pituitary cells [12,13] may confirm the present results. Our previous studies [9] demonstrating the ubiquitous presence of inhibin $A subunit mRNA by a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method in all of the human pituitary adenomas, regardless of their hormone production, was the strongest indicator of the presence of activin A in all human pituitary adenomas. The difference in activin immunostaining observed in the present study may therefore simply reflect the difference in the concentration of activin A present in the tissues studied.…”

“…Although their endocrine, autocrine or paracrine roles have been suggested [6], the evidence has been scarce and inconsistent as to the presence or absence, and the subtype of inhibins and activin present in the normal human pituitary as well as in adenoma tissues [7][8][9]. So far, Alexander and Klibanski detected inhibin a subunit mRNA in human gonadotropinoma [7] and Haddard et al reported the presence of f3, but not I A subunit mRNA, in gonadotropinomas [8].…”