Loss of annexin A1 disrupts normal prostate glandular structure by inducing autocrine IL-6 signaling

Junichi Inokuchi, Alice Lau, Darren R. Tyson, David K. Ornstein

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Annexin A1 (ANXA1) expression is commonly reduced in premalignant lesions and prostate cancer, but a causal relationship of ANAX1 loss with carcinogenesis has not been established. ANXA1 levels have been shown to inversely correlate with interleukin 6 (IL-6) expression in other cell types and IL-6 has been suggested to enhance prostate cancer initiation and promotion. To investigate whether loss of ANXA1 may contribute to prostate carcinogenesis, ANXA1 expression was reduced using RNA interference in non-tumorigenic human prostatic epithelial cells (RWPE-1/rA1). No effect on morphology, apoptosis, migration or anchorage-dependent or -independent growth was detected. However, IL-6 mRNA and secreted protein levels were elevated in RWPE-1/rA1 cells. In addition, re-expression of ANXA1 in these cells suppressed IL-6 secretion, and altering ANXA1 levels in prostate cancer cells had similar effects on IL-6. The effects of ANXA1 loss and increased IL-6 expression on prostate epithelium were examined using an assay of acinar morphogenesis in vitro. Acini formed by RWPE-1/rA1 cells had delayed luminal clearing and larger mean diameters than control cells. The RWPE-1/rA1 phenotype was recapitulated by treating control cells with recombinant IL-6 and was reversed in RWPE-1/rA1 cells by blocking IL-6 bioactivity. Taken together, these data support a direct role for decreased ANXA1 expression in prostate carcinogenesis and enhancing tumor aggressiveness via the upregulation of IL-6 expression and activity.

Original languageEnglish
Pages (from-to)1082-1088
Number of pages7
JournalCarcinogenesis
Volume30
Issue number7
DOIs
Publication statusPublished - Jul 15 2009

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Annexins
Annexin A1
Prostate
Interleukin-6
Prostatic Neoplasms
Carcinogenesis
RNA Interference
Morphogenesis
Up-Regulation
Epithelium
Epithelial Cells
Apoptosis
Phenotype
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Loss of annexin A1 disrupts normal prostate glandular structure by inducing autocrine IL-6 signaling. / Inokuchi, Junichi; Lau, Alice; Tyson, Darren R.; Ornstein, David K.

In: Carcinogenesis, Vol. 30, No. 7, 15.07.2009, p. 1082-1088.

Research output: Contribution to journalArticle

Inokuchi, Junichi ; Lau, Alice ; Tyson, Darren R. ; Ornstein, David K. / Loss of annexin A1 disrupts normal prostate glandular structure by inducing autocrine IL-6 signaling. In: Carcinogenesis. 2009 ; Vol. 30, No. 7. pp. 1082-1088.
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