Open AccessACSL 3 promotes intratumoral steroidogenesis in prostate cancer cells
Author(s) -
Migita Toshiro,
Takayama Kenichi,
Urano Tomohiko,
Obinata Daisuke,
Ikeda Kazutaka,
Soga Tomoyoshi,
Takahashi Satoru,
Inoue Satoshi
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13339
Subject(s) - prostate cancer , androgen , endocrinology , medicine , cancer research , testosterone (patch) , downregulation and upregulation , dehydroepiandrosterone , cancer , biology , chemistry , hormone , biochemistry , gene
Long‐chain acyl‐coenzyme A (CoA) synthetase 3 ( ACSL 3 ) is an androgen‐responsive gene involved in the generation of fatty acyl‐CoA esters. ACSL 3 is expressed in both androgen‐sensitive and castration‐resistant prostate cancer ( CRPC ). However, its role in prostate cancer remains elusive. We overexpressed ACSL 3 in androgen‐dependent LNC aP cells and examined the downstream effectors of ACSL 3. Furthermore, we examined the role of ACSL 3 in the androgen metabolism of prostate cancer. ACSL 3 overexpression led to upregulation of several genes such as aldo‐keto reductase 1C3 ( AKR 1C3 ) involved in steroidogenesis, which utilizes adrenal androgen dehydroepiandrosterone sulfate ( DHEAS ) as substrate, and downregulated androgen‐inactivating enzyme UDP ‐glucuronosyltransferase 2 ( UGT 2B ). Exposure to DHEAS significantly increased testosterone levels and cell proliferative response in ACSL 3‐overexpressing cells when compared to that in control cells. A public database showed that ACSL 3 level was higher in CRPC than in hormone‐sensitive prostate cancer. CRPC cells showed an increased expression of ACSL 3 and an expression pattern of AKR 1C3 and UGT 2B similar to ACSL 3‐overexpressing cells. DHEAS stimulation significantly promoted the proliferation of CRPC cells when compared to that of LNC aP cells. These findings suggest that ACSL 3 contributes to the growth of CRPC through intratumoral steroidogenesis (i.e. promoting androgen synthesis from DHEAS and preventing the catabolism of active androgens).