This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dabizzi, S. Articles by Arcangeli, A. Search for Related Content PubMed PubMed Citation Articles by Dabizzi, S. Articles by Arcangeli, A.

Luteinizing Hormone Increases Human Endometrial Cancer Cells Invasiveness through Activation of Protein Kinase A

Departments of Gynaecology, Perinatology, and Human Reproduction [S. D., I. N., P. B., E. B., M. G., M. M., G. S.], Experimental Pathology and Oncology [A. A.], Clinical Physiopathology [M. B.], and Human Pathology and Oncology [G. L. T.], University of Firenze, 50134 Firenze, Italy

Endometrial cancer (EC) is a hormone-dependent cancer that currently represents the most frequent malignancy of the female reproductive tract. The involvement of steroid hormones in its etiology and progression has been reported. The possibility that even gonadotropins (GT) could play a role in the genesis and establishment of EC is supported by the fact that specific receptors for the GT luteinizing hormone/human chorionic GT (LH/hCG) have been detected in a high percentage of ECs, and their expression is apparently related to the cancer grading. However, the precise mechanisms by which GTs might exert their effect on EC is still obscure. The aim of this study was to determine the effects of LH/hCG on the invasion potential of EC cell lines and primary human EC cells. Human recombinant (hr) LH (and hCG) induced a significant increase in cell invasiveness through Matrigel-coated porous membranes in an EC human cell line Hec1A, which expresses the LH/hCG receptor. This effect turned out to depend on hrLH binding to its specific receptors and to the subsequent activation of protein kinase A (PKA). Moreover the hrLH-induced increase in Hec1A invasiveness relied upon a PKA-dependent functional activation of ß₁ integrin receptors, as well as the subsequent induction of matrix metalloproteinase-2 secretion in its active form. The same mechanisms were also found to be operative in primary EC cells. In fact, a significant percentage of primary ECs expressed the LH/hCG receptor, and hrLH addition to primary EC cells, which expressed the specific receptors produced an increase in cell invasiveness only in those tumor cells possessing the specific receptors. This effect was also dependent on PKA activity. We conclude that LH/hCG can regulate EC cells invasiveness, and this result provides a rationale for the use of inhibitors of LH secretion such as GnRH analogues in the treatment of EC.

This article has been cited by other articles:

				J.-H. Choi, K.-C. Choi, N. Auersperg, and P. C.K. Leung Gonadotropins Activate Proteolysis and Increase Invasion through Protein Kinase A and Phosphatidylinositol 3-Kinase Pathways in Human Epithelial Ovarian Cancer Cells. Cancer Res., April 1, 2006; 66(7): 3912 - 3920. [Abstract] [Full Text] [PDF]

				R. A. Cardone, A. Bagorda, A. Bellizzi, G. Busco, L. Guerra, A. Paradiso, V. Casavola, M. Zaccolo, and S. J. Reshkin Protein Kinase A Gating of a Pseudopodial-located RhoA/ROCK/p38/NHE1 Signal Module Regulates Invasion in Breast Cancer Cell Lines Mol. Biol. Cell, July 1, 2005; 16(7): 3117 - 3127. [Abstract] [Full Text] [PDF]

				A. Cherubini, G. Hofmann, S. Pillozzi, L. Guasti, O. Crociani, E. Cilia, P. Di Stefano, S. Degani, M. Balzi, M. Olivotto, et al. Human ether-a-go-go-related Gene 1 Channels Are Physically Linked to {beta}1 Integrins and Modulate Adhesion-dependent Signaling Mol. Biol. Cell, June 1, 2005; 16(6): 2972 - 2983. [Abstract] [Full Text] [PDF]

				E. Lastraioli, L. Guasti, O. Crociani, S. Polvani, G. Hofmann, H. Witchel, L. Bencini, M. Calistri, L. Messerini, M. Scatizzi, et al. herg1 Gene and HERG1 Protein Are Overexpressed in Colorectal Cancers and Regulate Cell Invasion of Tumor Cells Cancer Res., January 15, 2004; 64(2): 606 - 611. [Abstract] [Full Text] [PDF]