Expression of the inhibin/activin subunits (-α, -βA and -βB) in normal and carcinogenic endometrial tissue: Possible immunohistochemical differentiation markers

Worbs, Silvia; Shabani, Naim; Mayr, Doris; Gingelmaier, Andrea; Makrigiannakis, Antonis; Kühn, Christina; Jeschke, Udo; Kupka, M.; Friese, Klaus; Mylonas, Ioannis

doi:10.3892/or.17.1.97

Cited by 23 publications

(33 citation statements)

References 26 publications

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“…using univariate analysis (¯2 test) revealed a significant association of inhibin-· immunolabeling with histological grading, FIGO stages and myometrial invasion (Table I). Interestingly, in poorly-differentiated endometrioid adenocarcinomas the expression of inhibin-· was down-regulated, confirming previous results (23,25,40).…”

Section: Resultssupporting

confidence: 80%

“…Immunohistochemistry was performed using a combination of pressure cooker heating and the standard streptavidin-biotin-peroxidase complex by using the mouse-IgG-Vectastain Elite ABC kit (Vector Laboratories, Burlingame, CA, USA) as previously described (23,24). The mouse monoclonal antibody used for the experiments was the inhibin-·, clone R1, monoclonal mouse IgG2a, diluted in PBS 1:50 as previously described (23)(24)(25).…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, they have also been detected in endocrine tumors (19), including ovarian (19)(20)(21), endometrial (22)(23)(24)(25)(26) and breast cancer tissue (27,28). Moreover, their differential expression has suggested an important role in malignant cell transformation (19,22,23,25). The inhibin-· subunit was recently demonstrated to be an independent prognostic parameter in a large cohort analysis of 302 human endometrial carcinomas (23).…”

Section: Introductionmentioning

confidence: 99%

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Inhibin-α subunit expression in uterine endometrioid adenocarcinomas and endometrial cancer cell lines: a potential prognostic factor

Mylonas

2011

Int J Mol Med

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Abstract. Inhibins/activins are secreted polypeptides of the transforming growth factor-ß superfamily, forming a family of dimeric, disulphide-linked proteins. Inhibins are composed of an ·-subunit and one of two possible ß-subunits. Both inhibins and activins have substantial roles in human reproduction and in endocrine-responsive tumors. However, the prognostic significance and clinical implications of the inhibin-· subunits in uterine endometrioid adenocarcinomas is still not clearly defined. A series of 231 uterine endometrioid adenocarcinomas of a previous well-characterized cohort were re-evaluated for the expression of the inhibin-· subunit and correlated with several clinicopathological characteristics and clinical outcome. Additionally, several endometrial epithelial cell lines (Ishikawa plus and minus, HEC-1A, HEC-1B and RL95-2) were analyzed for the expression of this subunit using immunohistochemical and molecular biological techniques. A significant association between the inhibin-· subunit and histological grade, surgical staging and myometrial invasion was demonstrated. Survival analysis demonstrated that inhibin-· immunoreactivity significantly affected progression-free, cause-specific and overall survival of patients with endometrioid adenocarcinomas. The analyzed endometrial cancer cell lines can also synthesize this subunit. Inhibin-· seems to have a substantial role in the carcinogenesis and pathology of uterine endometrioid carcinomas, and might be used as a marker to identify highrisk patients and may aid in the selection of patients for a more aggressive adjuvant therapy. Since uterine cancer cell lines express the inhibin-· subunit, they constitute adequate in vitro models for assessing its function in endometrial carcinogenesis. However, further research is warranted to elucidate the possible implications of inhibin-· in endometrial carcinogenesis.

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Section: Resultssupporting

confidence: 80%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibin-α subunit expression in uterine endometrioid adenocarcinomas and endometrial cancer cell lines: a potential prognostic factor

Mylonas

2011

Int J Mol Med

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“…Conservation of these residues in all TGF-β super family ligands suggests a common biosynthetic pathway governing the dimer assembly [25]. Aberrant expression in the levels of subunits and its receptors has been reported in various disease conditions [26][27][28][29][30]. This makes critical to understand the subunits synthesis, assembly, secretion and functions of inhibins under a variety of physiological and pathophysiological conditions.…”

Section: Historical Background Of Inhibins Discoverymentioning

confidence: 99%

New targets for old hormones: inhibins clinical role revisited [Review]

2011

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Abstract. Inhibins are gonadal peptide hormones belonging to the transforming growth factor-β (TGF-β) superfamily that regulate the pituitary follicle stimulating hormone (FSH) secretion by negative feedback mechanisms. It is evident that the understanding of inhibins function in the hypothalamic-pituitary-gonadal axis will provide insights into physiology and pathology of the gonadal function. In recent years, a great deal of attention has been focussed on clinical relevance of measuring circulating inhibins in normal and disease state. The past few years also have witnessed the emergence and discovery of extra pituitary action of inhibins that might provide further insights into the underlying diseases like cancer especially in the reproductive axis and various other new endocrine target organs. In this review after systematic analysis of literature, we discuss briefly the known and recent advances in function of these hormones highlighting also its structure, production and mechanisms of signal transduction. Also this review discusses about the physiological relevance of inhibin association in the normal function to the development of reproductive cancers. Finally, we describe evidence from various emerging studies that inhibins make an important contribution to other physiological functions apart from reproduction which reveals new endocrine target organs of inhibins. The emerging view is inhibin participates in multiple ways to regulate the function in different cell types and still complete repertoire of its actions is under investigation. Key words: Inhibin, Transforming growth factor, Ovarian cancer, Activins, BetaglycanMAMMAliAn reproduction is intricate, highly ordered and is coordinated by assorted neural, neuroendocrine, endocrine, autocrine and paracrine cell-cell communication pathways. Many of the pioneering discoveries meticulously demonstrated the roles of hypothalamic gonadotropin releasing hormone (GnRH) that stimulates pituitary gonadotropins such as follicle stimulating hormone (FSH) and leutinizing hormone (LH), which directly control gonadal functions. Subsequent breakthroughs in the advancement of molecular biology and in understanding signal transduction mechanisms suggested involvement of various cytokines and growth factors at each level of the hypothalamic-pituitary-gonadal axis in the paracrine/autocrine control of different programmed reproductive events. Members include inhibins and activins, belonging to the transforming growth factor (TGF-β) super family and follistatin (FS), a structurally distinct though functionally related molecule. It has been more than 70 years since the identification of negative feedback control of pituitary FSH secretion by inhibins. These factors also were shown to act in autocrine, endocrine or paracrine manner within the reproductive tissues, but the identification of specific pathways in different cellular context along the gonadal axis is still quite unclear and should thus be further investigated. The discovery process of extra pituitary action of ...

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“…The inhibin subunits have been detected in female endocrine tumours, suggesting important roles in malignant cell transformation (16)(17)(18)(19)(20). However, one of the most intriguing functions of the inhibin-α subunit is its tumour-suppressor activity (19), which was first identified after functional deletion of the inhibin-α gene in mice (21).…”

Section: Introductionmentioning

confidence: 99%

Inhibin-α subunit in normal and malignant human cervical tissue and cervical cancer cell lines

Mylonas

Dian²

2011

Oncol Rep

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Abstract. Inhibins are dimeric glycoproteins composed of an α-subunit and one of two possible β-subunits (βA or βB), with substantial roles in human reproduction and in endocrineresponsive tumours. Four normal cervical tissue samples together with 10 specimens of well-differentiated squamous cervical cancer and adenocarcinoma of the cervix were immunohistochemically analysed for the expression of the inhibin-α subunit. Additionally, two cervical carcinoma cell lines (HeLa and CaSKi) were analysed with immunofluorescence and RT-PCR for the expression of the inhibin-α subunit. We demonstrated for the first time an immunolabelling of the inhibin-α subunit in normal and malignant cervical tissue, as well as cervical cancer cells. However, the immunoreactive reaction was albeit weak and mostly confined to mitotic cells in the analysed cervical tissues. Additionally, the expression pattern of this subunit was rather inconsistent. Therefore, the immunohistochemical evaluation of this subunit in cervical tissue cannot be used as a prognostic marker as suggested for endometrial cancer. However, since the expression of the inhibin-α subunit is minimal in HeLa cells as assessed by immunofluorescence and RT-PCR, the CaSKi cell line might be a better model for further functional experiments regarding cervical pathogenesis.

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Expression of the inhibin/activin subunits (-α, -βA and -βB) in normal and carcinogenic endometrial tissue: Possible immunohistochemical differentiation markers

Cited by 23 publications

References 26 publications

Inhibin-α subunit expression in uterine endometrioid adenocarcinomas and endometrial cancer cell lines: a potential prognostic factor

Inhibin-α subunit expression in uterine endometrioid adenocarcinomas and endometrial cancer cell lines: a potential prognostic factor

New targets for old hormones: inhibins clinical role revisited [Review]

Inhibin-α subunit in normal and malignant human cervical tissue and cervical cancer cell lines

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