Development and differentiation of the mammary gland is dependent on the appropriate temporal expression of both systemically acting hormones and locally produced growth factors. A large body of evidence suggests that molecular crosstalk between these hormonal and growth factor axes are crucial for appropriate cell and tissue function. Two of the most important trophic factors involved in this process are the oestrogen (E) and insulin-like growth factor (IGF) molecular axes. The reciprocal crosstalk that exists between these pathways occurs at transcriptional/posttranscriptional and translational/post-translational levels regulates the expression and activity of genes involved in this process .In a clinical context an important consequence of such crosstalk in the mammary gland is the role which it may play in the aetiology, maintenance and development of breast tumours. Although oestradiol (E 2 ) acting through oestrogen receptors and (ER / ) is important for normal mammary gland function it can also provide a mitogenic drive to ER+ breast tumours. Therefore over several years anti-oestrogen therapeutic regimens in the form of selective oestrogen receptor modulators (SERMs -e.g. tamoxifen), aromatase inhibitors (AI e.g. anastrozole) or selective oestrogen receptor down regulators (SERDs -e.g. fulvestrant) have been used in an adjuvant setting to control tumour growth. Although initial response is usually encouraging, large cohorts of patients eventually develop resistance to these treatments leading to 2 tumour recurrence and poor prognosis .Although there are potentially many routes by which breast cancer (BC) cells could escape anti-oestrogen based therapeutic strategies one of the most studied is the putative growth factor mediated activation of ER(s). Such E-independent activation of ER could provide a route of escape from classical anti-oestrogen based therapeutic strategies. Because of this growth factor modulation of ER activity has been an intensively studied route of molecular crosstalk in the mammary gland. The insulin-like growth factors (IGF-1 and -2) are amongst the most potent mitogens for mammary epithelial cells and there is accumulating evidence that they interact with the E 2 axis to regulate mitogenesis, apoptosis, adhesion, migration and differentiation of mammary epithelial cells. Such interactions are also bi-directional and E 2 has been shown to regulate the expression and activity of IGF axis genes with the general effect of sensitising breast epithelial cells to the actions of IGFs and insulin. In this short review we discuss the evidence for the involvement of crosstalk between the insulin-like growth factor (IGF) and oestrogen axes in the mammary gland and comment on the relevance of such studies in the aetiology and treatment of BC.

Background BRCA1/2 pathogenic variants have become associated with familial breast and ovarian cancers, and hereditary cancer‐predisposition syndrome. With advances in molecular biology, BRCA profiling facilitates early diagnosis and the implementation of preventive and therapeutic strategies. The genes exhibit variable prevalence among different individuals and moderate interpretation complexity. BRCA deficiency is instrumental in cancer development, affects therapeutic options and is instrumental in drug resistance. In addition, BRCA1/2 profile is diverse across different groups and has been associated with the “founder effect” in certain populations. Methods In this review, we aim to detail the spectrum of BRCA1/2 variants and their associated risk estimates. Results The relationship between BRCA1/2 and hereditary and familial cancers is indisputable, yet BRCA screening methods are beset with limitations and lack clinical confidence. Conclusion This review emphasizes the importance of screening BRCA genetics, in addition to their clinical utility. Furthermore, founder variants are anticipated in the Saudi population.

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Human dental pulp cells (DPCs), which are known to contain a subset of stem cells capable of reforming a dentin and pulp-like complex upon in vivo transplantation, were isolated from third molars of three healthy donors and differentiated to a matrix mineralisation phenotype using by culture in dexamethasone and l-ascorbic acid. qRT-PCR analysis of insulin-like growth factor ( IGF) axis gene expression indicated that all genes, except insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein-1 ( IGFBP-1), were expressed in DPCs. During differentiation upregulation of insulin-like growth factor binding protein-2 (IGFBP-2) and downregulation of insulin-like growth factor binding protein-3 (IGFBP-3) expression was observed. Changes in IGFBP-2 and IGFBP-3 mRNA expression were confirmed at the protein level by ELISA of DPC conditioned medium functional analysis indicated that IGF1 stimulated the differentiation of DPCs and that the activity of the growth factor was enhanced by pre-complexation with IGFBP-2 but inhibited by pre-complexation with IGFBP-3. Therefore changes in IGFBP-2 and -3 expression during differentiation form part of a co-ordinated functional response to enhance the pro-differentiative action of IGF1 and represent a novel mechanism for the regulation of DPC differentiation.