In vitro studies of a prolactin antagonist, hPRL-G129R in human breast cancer cells.

  • Authors:
    • P Ramamoorthy
    • R Sticca
    • T E Wagner
    • W Y Chen
  • View Affiliations

  • Published online on: January 1, 2001     https://doi.org/10.3892/ijo.18.1.25
  • Pages: 25-57
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Abstract

Human prolactin (hPRL) has been shown to be one of the important survival/growth factors that promotes the proliferation of breast cancer cells in an autocrine/paracrine manner. In our recent studies, we demonstrated that a hPRL antagonist with a single amino acid substitution mutation (hPRL-G129R) was able to inhibit breast cancer cell proliferation via induction of apoptosis (1). In this study three independent yet related experiments were carried out regarding the effects of hPRL-G129R in breast cancer cells. We investigated the possible mechanism(s) of hPRL-G129R induced apoptosis in breast cancer cells. It is well documented that transforming growth factors (TGF) in conjunction with hormones such as estrogen and PRL play a major role in modulating the proliferation and apoptosis of mammary cells. We first investigated the relationships between hPRL/hPRL-G129R and TGFs. We show that hPRL is able to down-regulate TGF beta 1 (apoptotic factor) secretion and up-regulate TGF alpha (survival factor) secretion in a dose-dependent manner in T-47D cells. More importantly the hPRL antagonist up-regulates TGF beta 1 and down-regulates TGF alpha secretion. When hPRL-G129R was applied together with hPRL, it blocked the effects of hPRL. Secondly, we tested the possible involvement of caspases in hPRL-G129R induced apoptosis. We have shown that caspase-3 is activated by hPRL-G129R at a concentration of 250 ng/ml in T-47D breast cancer cells. Thirdly, we explored the additive effects of an anti-neoplastic drug, cisplatin, with the hPRL-G129R in T47D breast cancer cells. We show that cisplatin and hPRL-G129R when applied together resulted in about 40% growth inhibition in T-47D cells.

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January 2001
Volume 18 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ramamoorthy P, Sticca R, Wagner T and Chen W: In vitro studies of a prolactin antagonist, hPRL-G129R in human breast cancer cells.. Int J Oncol 18: 25-57, 2001.
APA
Ramamoorthy, P., Sticca, R., Wagner, T., & Chen, W. (2001). In vitro studies of a prolactin antagonist, hPRL-G129R in human breast cancer cells.. International Journal of Oncology, 18, 25-57. https://doi.org/10.3892/ijo.18.1.25
MLA
Ramamoorthy, P., Sticca, R., Wagner, T., Chen, W."In vitro studies of a prolactin antagonist, hPRL-G129R in human breast cancer cells.". International Journal of Oncology 18.1 (2001): 25-57.
Chicago
Ramamoorthy, P., Sticca, R., Wagner, T., Chen, W."In vitro studies of a prolactin antagonist, hPRL-G129R in human breast cancer cells.". International Journal of Oncology 18, no. 1 (2001): 25-57. https://doi.org/10.3892/ijo.18.1.25