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Endocrinology Vol. 141, No. 4 1571-1584
Copyright © 2000 by The Endocrine Society

ARTICLES

Autocrine Human Growth Hormone Enhancement of Human Mammary Carcinoma Cell Spreading Is Jak2 Dependent1

Karmal K. Kaulsay, Hichem C. Mertani, Kok-Onn Lee and Peter E. Lobie

Department of Medicine, National University of Singapore (K.K.K., K.O.L.), Singapore 119074; and Institute of Molecular and Cell Biology (H.C.M., P.E.L.), Singapore 117069, Republic of Singapore

Address all correspondence and requests for reprints to: Dr. Peter E. Lobie, Institute of Molecular and Cell Biology, 30 Medical Drive, 117609 Singapore, Republic of Singapore. E-mail: mcbpel{at}mcbsgs1.imcb.nus edu.sg.

We investigated the role of autocrine production of human (h) GH in the attachment and spreading of mammary carcinoma cells in vitro. We used a previously described model system for the study of the autocrine/paracrine role of GH in which the hGH gene (MCF-hGH) or a translation-deficient hGH gene (MCF-MUT) was stably transfected into MCF-7 cells. No differences in attachment to a collagen matrix between MCF-hGH and MCF-MUT cells were observed in either serum-free medium (SFM) or medium containing exogenous hGH, 5% serum, or 10% serum. In contrast, MCF-hGH cells spread more rapidly on a collagen matrix than did MCF-MUT cells. Exogenous hGH and 10% serum interacted with autocrine production of hGH in an additive manner to increase cell spreading. MCF-hGH cells formed filipodia and stress fibers earlier than MCF-MUT cells during the process of cell spreading and possessed marked differences in morphology after spreading. MCF-MUT cells displayed uniform and symmetrical formation of stress fibers, whereas MCF-hGH cells displayed irregular and elongated stress fiber formation. The level of cytoplasmic phosphotyrosine was increased in MCF-hGH compared with MCF-MUT cells during spreading and displayed colocalization with Janus kinase 2 (JAK2). Basal JAK2 tyrosine phosphorylation was increased, and it increased further on spreading in MCF-hGH cells compared with MCF-MUT cells. Transient transfection of JAK2 complementary DNA resulted in interaction with autocrine hGH to increase the rate of cell spreading in MCF-hGH cells compared with MCF-MUT cells. Treatment with a selective JAK2 tyrosine kinase inhibitor (AG 490) reduced the rate of MCF-hGH cell spreading to the rate of MCF-MUT cell spreading. Thus, we conclude that autocrine production of hGH enhances the rate of mammary carcinoma cell spreading in a JAK2-dependent manner.




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