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Calcitonin increases invasiveness of prostate cancer cells: Role for cyclic AMP‐dependent protein kinase A in calcitonin action
Author(s) -
Sabbisetti Venkata S.,
Chirugupati Srinivasulu,
Thomas Shibu,
Vaidya Kedar S.,
Reardon Dean,
ChirivaInternati Maurizio,
Iczkowski Kenneth A.,
Shah Girish V.
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21158
Subject(s) - calcitonin , endocrinology , prostate , protein kinase a , medicine , cancer , kinase , biology , chemistry , microbiology and biotechnology
Calcitonin (CT) is synthesized and secreted in prostate epithelium, and its secretion from malignant prostates is several‐fold higher than from benign prostates. CT receptor (CTR) is expressed in malignant prostate epithelium, and its activation stimulates growth of prostate cancer (PC) cells via activation of adenylyl cyclase and calcium/phospholipid pathways. To identify the role of “CT System” in prostate cancer, we tested the expression of CT and CTR mRNAs in invading tumor cells of prostate cancer specimens. The effect of CT on in vitro invasion of PC cell lines and on activation of gelatinases was also examined. The cells of primary tumors and those invading stroma co‐expressed CT/CTR mRNAs. Exogenously added CT increased in vitro invasion of PC cell lines and caused a rapid, several‐fold but transient increase in protein kinase A activity. In contrast, anti‐CT serum caused a dose‐dependent inhibition of in vitro invasion of PC‐3M cells. CT also increased the concentration and activities of MMP‐2 and MMP‐9. Rp.cAMP, a competitive inhibitor of cAMP‐dependent protein kinase A, myristoylated protein kinase A inhibitory peptide (PKI) as well as the expression of dominant negative form of PKA all attenuated basal in vitro invasion of PC‐3M cells, and CT could not increase in vitro invasiveness in their presence. These results suggest that overexpression of “CT System” in invasive PC tumors significantly contributes to increased invasiveness of prostate cancer cells. The action of CT may be mediated by protein kinase A signaling, which subsequently leads to increased cell invasion and secretion of gelatinases. © 2005 Wiley‐Liss, Inc.