cyclin-d1 and Seminoma

Seminoma, originated from carcinoma in situ cells (CIS), is one of the main causes of cancer in young men. Postpubertal development of these testicular germ cell tumors suggests a hormone-sensitive way of CIS cell proliferation induction. Using the unique seminoma TCam-2 cell line, we demonstrate that both estradiol and testosterone can stimulate TCam-2 cell proliferation in the absence of the estradiol receptor ERα. We establish that estradiol can activate GPER-cAMP/PKA signalling pathway. TCam-2 cells express ERα36, a truncated isoform of the canonical ERα receptor, the expression of which is rapidly induced after estrogen treatment in a GPER-dependent manner. ERα36 knockdown indicates that ERα36 is (i) a downstream target of E(2)-activated GPER/PKA/CREB pathway, (ii) required for estradiol-dependent EGFR expression, (iii) necessary for cell proliferation. Colocalization of ERα36 with cytoskeleton microfilaments suggests a role of estrogens in cell motility. Our results highlight the functional role of ERα36 in context of seminoma cell proliferation and the importance of testing ERα36 in vivo as a possible future prognostic marker.

Topics: Cell Line, Tumor; Cell Nucleus; Cell Proliferation; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cyclin D1; ErbB Receptors; Estradiol; Estrogen Receptor alpha; Estrogens; Gene Expression; Gene Expression Regulation; Humans; Male; Phosphorylation; Protein Isoforms; Protein Transport; Receptors, Estrogen; Receptors, G-Protein-Coupled; Seminoma; Signal Transduction; Testosterone