Expression and function of ATIP/MTUS1 in human prostate cancer cell lines

Abstract

The results support our earlier proposal in normal cell lines that ATIP is an important component of the cellular response to AT(2)-receptor activation. The results further suggest that a critical level of ATIP is required to mediate the effect of AT(2)-receptor activation to inhibit EGF mediated increases in cell growth. They also suggest that EGF may in part induce cell growth by suppressing the level of ATIP expression.

The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer

“…Previously, we have examined the correlation between ATIP1 mRNA expression and rate of proliferation in relatively slow growing androgen-dependent prostate cancer cells, LNCaP, and fast growing androgen-independent PC3 prostate cancer cells [10]. We hypothesized at the time that ATIP expression maybe inversely correlated with rate of proliferation in the two prostate cancer cell lines as similar relationships had been identified in both pancreatic and breast cancers [9,12].…”

“…Moreover, ATIP3 mRNA was re-expressed to higher levels than ATIP1. At this time the role of ATIP3 in prostate cancer is unknown; however, its role in breast cancer has been identified and it appears to slow mitosis and inhibit cell proliferation [9]; therefore, its function appears to be similar to that of ATIP1 [5,10,12]. This suggestion received support in an in vitro study where we used siRNA techniques to knock-down both ATIP1 and ATIP3 expression in LNCaP and PC3 cells using silencing probes that targeted the interacting domain that is present within all ATIP isoforms [10].…”

“…More recently, we identified ATIP expression in androgen-dependent (LNCaP) and androgen-independent (PC3) prostate cancer cells where we found ATIP1 to be a negative regulator of cell growth acting in concert with the AT 2 -receptor. ATIP1 over-expression reduced basal and EGF mediated ERK phosphorylation in PC3 cells whereas ATIP silencing increased the basal rate of DNA synthesis in PC3 cells and the sensitivity of LNCaP cells to the mitogenic effects of EGF [10]. …”

“…As ATIP appears to play an important role in human prostate cancer cell growth, we have extended our recent work [10] to determine the expression and localization of ATIP using immunohistochemical techniques in fixed prostate cancer cells and paraffin-embedded human prostatic biopsy materials containing benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), a premalignant state, and a range of prostate cancer grades. In addition, we extended our studies of the expression of ATIP1 and ATIP3 mRNA in normal and cancerous prostatic cell lines and provide further information on normal human prostate biopsy material using QPCR.…”

Function and expression of ATIP and its variants in cardiomyoblast cell line H9c2

“…What is known is that ATIP3 expression decreases in invasive breast tumours, 44 and overexpression of this variant, much like the effects of ATIP1 over-expression in normal 36 and prostate cancer cells, 46 reduces cell division. 44 Moreover, ATIP3 has been shown to be a mitotic spindle-associated protein in breast cancer cells and prolongs mitosis.…”