ANXA7 expression represents hormone-relevant tumor suppression in different cancers.
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(+/-) 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.
Srivastava
Meera
M
Department of Anatomy, Physiology and Genetics, and Institute for Molecular Medicine, Uniformed Services University School of Medicine (USUHS), Bethesda, MD, USA. msrivastava@usuhs.mil
Torosyan
Yelizaveta
Y
Raffeld
Mark
M
Eidelman
Ofer
O
Pollard
Harvey B
HB
Bubendorf
Lukas
L
D000818:Animals; D017310:Annexin A7 / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology*; D040081:Protein Array Analysis; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis
D017310:Annexin A7; C480504:Anxa7 protein, mouse; D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; C102837:Nkx3-1 protein, mouse; D014157:Transcription Factors