Stanniocalcin 2 expression is regulated by hormone signalling and negatively affects breast cancer cell viability in vitro

Abstract

Stanniocalcin 1 (STC1) and STC2 are secreted, homodimeric glycoproteins that share 30% amino acid sequence identity. Breast tumour gene profiling studies have demonstrated significantly upregulated STC2 expression in hormoneresponsive positive breast tumours; therefore, the purpose of this study was to investigate STC2 hormonal regulation and function in breast cancer cells. Here we report that STC2 is expressed in a number of human breast cancer cell lines, regardless of their oestrogen (E 2 ) and progesterone (P4) receptor status, and its expression is readily detectable in human and mouse mammary gland tumours. Besides E 2 , retinoic acid (RA) and P4 play an important role in the regulation of STC2 expression, not only in MCF-7 but also in other breast cancer and non-breast cell lines. The expression of the related hormone, STC1, is not affected by the above hormones in breast and endometrial cancer cell lines implying a fundamental difference in regulation in cancer cell lines. The induction of STC2 expression by E 2 and RA occurs at the transcriptional level but through intermediary transcription factors. The STC2 proximal promoter region is not responsible for hormonal induction, but exhibits a high basal transcriptional activity. Constitutive STC2 expression in human breast cancer cell lines resulted in significant impairment of cell growth, migration and cell viability after serum withdrawal. In conclusion, STC2 is a downstream target of E 2 , P4 and RA signalling pathways. In hormone receptor negative cell lines it can function in a paracrine/autocrine fashion to reduce cell proliferation.

Clinicopathological significance of stanniocalcin 2 gene expression in colorectal cancer

“…29 Additionally, it was reported that STC2 expression was sporadically abrogated in human cancer cells by transcriptional silencing associated with CpG island promoter hypermethylation. 36 Constitutive expression of human STC2 in transgenic mice acts as a potent growth inhibitor in vivo and results in a significant reduction of intramembranous and endochondral bone development, as well as high neonatal morbidity.…”

“…It was reported that the STC1 gene is associated with some cancers. [17][18][19][20][21][22][23][24] STC2 was reported to be associated with breast cancer, [25][26][27][28][29] ovarian cancer 30 and renal cell carcinoma. 31 However, the relationship between STC2 expression and clinicopathological factors in colorectal cancer has not yet been investigated.…”

Human stanniocalcin-1 or -2 expressed in mice reduces bone size and severely inhibits cranial intramembranous bone growth

“…The EGPs were pooled for each genotype from a particular litter for RNA extraction or protein lysates which were generated by homogenization in lysis buffer and protein concentration was determined using a Bradford assay (BioRad) (Raulic et al 2008). Western blot analysis was performed as described previously using 50 lg protein per lane, probed with PCNA antibody (Cell Signaling #2586), or cleaved caspase-3 (Asp175) antibody (Cell Signaling #9661) followed by probing with antibody against b-actin as a loading control (Sigma A2066) (Raulic et al 2008). The positive control lysate for apoptosis and detection of cleaved caspase-3 fragments was generated by an overnight treatment of primary mouse ovarian cells in culture with cycloheximide (50 lg/ml).…”

β3‐Tubulin is induced by estradiol in human breast carcinoma cells through an estrogen‐receptor dependent pathway

“…4b). The concentration employed to inhibit ER has been defined in numerous reports [Chambliss and Shaul, 2002;Barnett et al, 2008;Raulic et al, 2008]. Exposure of cells to 100 nM of fulvestrant alone did not significantly modify the gene expression level of b3-tubulin or PS2.…”