Their mutational rate is lower compared to other subtypes, and the most frequently reported mutations relate to PIK3CA, GATA3, and MAP3K1
. Luminal A tumors are characterized by low histological grade and are diploid in contrast to luminal B tumors which are high-grade and frequently aneuploid.
Formerly known as an AXIN1 inter-actor in the c-Jun NH(2)-terminal kinase pathway, MAP3K1 also takes part in the canonical Wnt signaling pathway, where it positively regulates the expression of Wnt target genes .
MAP3K1 functionally interacts with AXIN1 in the canonical Wnt signalling pathway.
Eight hours after RD cells were infected with EV71, the expression levels of c-Jun, c-Fos, IFN-[beta], MEKK1 (MAP3K1
), MLK3 (MAP3K11) and NIK (MAP3K14) revealed 2.08-6.12 fold enhancement, while other 19 genes (e.g.
New studies are underway to determine whether the inclusion of additional elements into existing models, especially Gail model, such as mammographic density, weight gain, serum level of steroid hormones, and genetic variations (SNP-single nucleotide polymorphisms) associated with breast cancer (including the genes CASP8, MAP3K1
, RAD51L1 and others) will improve the risk prediction (GARETH et al., 2007; WACHOLDER et al., 2010).
In contrast, mutations in MAP3K1
and its "sister" gene MAP2K4 occurred in about 16 percent of patients and were linked to a good response to aromatase inhibitors.
Four loci contained plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1) with no gene candidate at the 8q24 locus.
Variants in FGFR2 and MAP3K1 were each associated with increased breast cancer risk in BRCA2 mutation carriers, but not in BRCA1 carriers.
Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases.
(141) Tumors with the luminal A subtype are associated with MAP3K1
, GATA3, and PIK3CA mutations and may benefit from neoadjuvant aromatase inhibitors.
"MAP3K1 may hold the key to understanding how these various genes are connected," said Harry Ostrer, director of the Human Genetics Program at the Centre.
All of these individuals had a normal SRY gene, leading the researchers to suspect that MAP3K1 may influence the activity of that gene.