LATS2 is a modulator of estrogen receptor alpha.
Anticancer Res
; 33(1): 53-63, 2013 Jan.
Article
in En
| MEDLINE
| ID: mdl-23267128
ABSTRACT
BACKGROUND:
Estrogen Receptor α (ERα), a member of the nuclear receptor superfamily of transcription factors, plays a central role in breast cancer development. More than two-thirds of patients with breast cancer are ERα-positive; however, a proportion becomes resistant. Phosphorylation of ERα is one of the mechanisms associated with resistance to endocrine therapy. In a kinome screen, we have identified the large tumor suppressor homolog-2 (LATS2) as a potential kinase, acting on ERα. MATERIALS ANDMETHODS:
The role of LATS2 on activation of ERα transcription and its functional consequences was examined by various molecular and cellular biology techniques.RESULTS:
LATS2 co-localises with ERα in the nucleus. LATS2-silencing increases expression of ERα-regulated genes and inhibits proliferation. At the protein level, inhibition of LATS2 reduces the expression of cyclin-D1 and Nuclear Receptor Co-Repressor (NCoR) while increasing the expression of p27.CONCLUSION:
Identifying novel kinases which modulate ERα activity is relevant to therapeutics. LATS2 modulates ERα-regulated gene transcription, through direct and/or indirect interactions with ERα.
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Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Protein Serine-Threonine Kinases
/
Tumor Suppressor Proteins
/
Estrogen Receptor alpha
/
Neoplasms, Hormone-Dependent
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
Language:
En
Year:
2013
Type:
Article