Inhibin/activin-betaC and -betaE subunits in the Ishikawa human endometrial adenocarcinoma cell line.
BACKGROUND
Inhibins and activins are important regulators of the female reproductive system. Recently, two novel inhibin subunits, named betaC and betaE, have been identified and shown to be expressed in several human tissues. However, only limited data on the expression of these novel inhibin subunits in normal human endometrial tissue and endometrial adenocarcinoma cell lines exist.


METHODS
Samples of proliferative and secretory human endometrium were obtained from five premenopausal, non-pregnant patients undergoing gynecological surgery for benign diseases. Normal endometrial tissue and Ishikawa endometrial adenocarcinoma cell lines were analyzed by immunohistochemistry, immunofluorescence and RT-PCR.


RESULTS
Expression of the inhibin betaC and betaE subunits could be demonstrated at the protein level by means of immunohistochemical evaluation and at the transcriptional level by establishing a betaC- and betaE-specific RT-PCR analysis in normal human endometrial tissue and the parental Ishikawa cell line. Interestingly, in a highly de-differentiated subclone of the Ishikawa cell line lacking estrogen receptor expression, the expression of the inhibin-betaC subunit appeared strongly reduced.


CONCLUSIONS
Here, we show for the first time that the novel inhibin/activin-betaC and -betaE subunits are expressed in normal human endometrium and the estrogen receptor positive human endometrial carcinoma cell line Ishikawa using RT-PCR and immunohistochemical detection methods. Interestingly, the Ishikawa minus cell line (lacking estrogen receptor expression) demonstrated no to minimal expression of the betaC subunit as observed with immunofluorescence and RT-PCR, suggesting a possible hormone- dependency of this subunit in human endometrial cancer cells. Moreover, because the Ishikawa cell line minus is thought to be a more malignant endometrial cell line than its estrogen receptor positive counterpart, inhibin-betaC subunit might be substantially involved in the pathogenesis and malignant transformation in human endometrium.
Kimmich
Tanja
T
1st Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University Munich, Maistrasse 11, 80337 Munich, Germany.
Brüning
Ansgar
A
Käufl
Stephanie D
SD
Makovitzky
Josef
J
Kuhn
Christina
C
Jeschke
Udo
U
Friese
Klaus
K
Mylonas
Ioannis
I
D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism*; D054337:Cell Dedifferentiation; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000378:metabolism*; D004717:Endometrium / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D028322:Inhibin-beta Subunits / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C504186:INHBC protein, human; C504183:INHBE protein, human; D011960:Receptors, Estrogen; D028322:Inhibin-beta Subunits