Abstract
Abstract Objective To study the difference of serum FSH level between breast cancer and healthy people in postmenopausal women; To investigate the internal relations of FSH and the tumor clinical classfication ,lymph node metastasis, and the status of ER,PR,Her-2 and Ki67; To study the expression of FSHR in breast cancer cell line and breast cancer tissue ; To study whether rhFSH induce proliferation and metastasis of breast cancer cell line and the exact mechanism in vitro and in vivo. Method Part 1: Clinical datas of 187 postmenopausal women diagnosed of breast cancer and 374 postmenopausal healthy people were collected for statistic analysis. Part2: Two breast cancer cell line (Bcap-37 and MDA-MB-231) have been used to study whether the rhFSH induce proliferation and metastasis in vitro. Part3: In vivo study of the rhFSH whether to promote tumor proliferation.We established a postmenopausal animal model of Balb/c nu/nu mouse by ovariectomized (OVX). The experiment was divided into four groups: Sham , OVX control, using GnRha after OVX, using GnRHa followed rhFSH after OVX. Part 4: RT-PCR and Reverse-PCR has used to investigate the expression of FSHR in many breast cancer cell line. The expression of FSHR in 17 samples of breast tissue was also been detected by RT-PCR. Results Part1: The serum level of FSH ,LH in postmenopausal breast cancer were higher than postmenopausal healthy people( 61.83±1.475 vs. 48.13±1.256 IU/L;27.83±0.74 vs.23.88±0.6499 IU/L).FSH has a positive correlation with Ki67 and Her-2 expression in breast . Part2: It has been found that rhFSH could promote the Bcap-37 and MDA-MB-231cell proliferation regardless of whether low concentration (10 ng/mL) or high concentration (50 ng/mL) in vitro. The rhFSH induce the proliferation and metastasis by activated ERFR/ERK1/2 cell pathway. Part3: A high concentration of rhFSH (≈100IU/L) could promote breast cancer cell line Bcap-37 and MDA-MB-231 proliferation in vivo. Part4: The FSHR was not expressed in all of the breast cancer cells tested and breast cancer tissue. Conclusion Postmenupausal breast cancer patient favored a high serum gonadotropin level compared with healthy people.FSH has a positive correlation with the Her-2 and Ki 67expresssion in breast cancer. The rhFSH cound promote the proliferation and metastasis of breast cancer cell line Bcap-37 and MDA-MB-231 by activated the EGFR/ERK1/2 pathway. A high concentration of rhFSH (≈100IU/L) may also promote the proliferation of breast cancer cell line in vivo. However, there is no FSHR expression in breast cancer cell line and breast cancer tissue. Further studies are needed to charlify the exact mechanism between FSH and postmenopausal breast cancer. Note: This abstract was not presented at the meeting. Citation Format: Yi-Ding Chen. Preliminary study of the follicle-stimulating hormone α/β and the pathogenesis of postmenopausal breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 624. doi:10.1158/1538-7445.AM2014-624
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