ANXA7 expression represents hormone‐relevant tumor suppression in different cancers

Abstract

Tumor suppressor function of ubiquitously expressed Annexin-A7, ANXA7 (10q21) that is involved in exocytosis and membrane fusion was based on cancer prone phenotype in Anxa7(1/2) mice as well as ANXA7 role in human prostate and breast cancers. To clarify ANXA7 biomarker and tumor suppressor function, we analyzed its expression pattern in comparison to the prostate-specific biomarker NKX3.1. Immunohistochemistry-based ANXA7 and NKX3.1 protein expression was analyzed on human tissue microarrays of 4,061 specimens from a wide spectrum of the histopathologically well-characterized tumors in different stages compared to corresponding normal tissues. Decreased ANXA7 expression was mostly associated with high invasive potential in multiple tumors. Although some metastases retained relatively high ANXA7 rates compared to primary cancer tissues, the lymph node metastases from different sites (including prostate and breast) had decreased ANXA7 expression in comparison to the intact lymphatic tissues. Major ANXA7 downregulation pattern was deviated in tumors of glandular (especially neuroendocrine) origin. ANXA7 and NKX3.1 proteins were synexpressed in the male urogenital system and adrenal gland. Gene expression profiling in prostate and breast cancers (SMD) revealed distinct hormone-related profiles for NKX3.1 and ANXA7, where ANXA7 expression correlated with steroid sulfatase which has a pivotal role in steroidogenesis. Abundant protein presence in adrenal gland and its loss in hormone-refractory prostate cancer indicated that ANXA7 can be relevant to steroidogenesis and androgen sensitivity in particular. With tumor suppressor pattern validated in different tumors, ANXA7 can be an attractive diagnostic and therapeutic target associated with the hormone and/or neurotransmitter-mediated modulation of tumorigenesis. ' 2007 Wiley-Liss, Inc.

Role of multi-hnRNP nuclear complex in regulation of tumor suppressor ANXA7 in prostate cancer cells

“…Showing a typical tumor suppressor gene pattern in our multitumor tissue microarray study, ANXA7 protein expression is consistently decreased in tumors (Srivastava et al, 2007). However, although reduced in androgen-resistant prostate cancers, ANXA7 is abundant in the adrenal gland, suggesting that its hormone-related expression could be coordinated with steroidogenesis and hormone sensitivity.…”

“…ANXA7 is specifically reduced in androgen-resistant prostate tumors (Srivastava et al, 2007). In the meantime, wild-type ANXA7 decreases and dominant-negative DN-ANXA7 increases low-molecular weight AR in androgen-sensitive LNCaP (Torosyan et al, 2009).…”

“…Human ANXA7 has shown a tumor suppressor role in multiple studies that involved prostate cancer (Srivastava et al, 2003(Srivastava et al, , 2007Torosyan et al, 2009). In addition, Anxa7( ± ) mice have a cancer-prone phenotype, leading to a spectrum of tumors including prostate cancer (Srivastava et al, 2003).…”

Annexin‐A7 protects normal prostate cells and induces distinct patterns of RB‐associated cytotoxicity in androgen‐sensitive and ‐resistant prostate cancer cells

“…4 However, exogenous WT-ANXA7 was capable of overcoming androgen-resistant status in vitro in both DU145 and PC3. By targeting AR, WT-ANXA7 represented a potential alternative to antiandrogens which may promote tumor invasiveness.…”

“…In addition to Ca 21 -activated GTPase activity as well as involvement in membrane fusion and exocytosis, ANXA7 demonstrated tumor suppressor function in murine model 1 and in human prostate and breast cancers. 2,3 Our large-scale study on ANXA7 protein expression in different cancers 4 identified a drastic ANXA7 loss in the hormone-refractory prostate cancers as well as an abundant ANXA7 presence in the adrenal gland, a major source of sex hormone precursors. Although tumor suppressor mechanisms of ANXA7 are not yet elucidated, these data suggested that ANXA7, which has androgen-receptor (AR) regulatory elements in its promoter, may be involved in the regulation of androgen-dependent cell survival in prostate cancer cells.…”