Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation

Deshmukh, Sachin Kumar; Srivastava, Sanjeev K.; Bhardwaj, Arun; Singh, Ajay P.; Tyagi, Nidhi; Marimuthu, Saravanakumar; Dyess, Donna L.; Zotto, Valeria Dal; Carter, James E.; Singh, Seema

doi:10.18632/oncotarget.3591

Cited by 92 publications

(110 citation statements)

References 54 publications

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“…About 80–90% of prostate cancer specimen indicate the signs of immune infiltration (55). Besides immune cells, cancer-associated fibroblasts (CAFs) present in TME also participate vigorously in growth and aggressiveness of the tumor by secreting several chemokines, cytokines, growth factors and other inflammatory mediators (56,57). CAFs communicate with cancer cells and immune cells through direct cell contact or by paracrine/exocrine signaling.…”

Section: Role Of Aberrantly-activated Signaling Pathways In Prostamentioning

confidence: 99%

Racial disparities in prostate cancer a molecular perspective

et al. 2017

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Prostate cancer incidence and mortality rates are remarkably higher in African-American men as compared to their European-Americans counterparts. Despite these recognitions, precise causes underlying such prevalent racial disparities remain poorly understood. Although socioeconomic factors could account for such differences up to a certain extent, it is now being increasingly realized that such disparity has a molecular basis. Indeed, several differences, including genetic polymorphism, gene mutations, epigenetic modifications, miRNAs alterations, etc., have been reported in malignant prostate tissues from patients of diverse racial backgrounds. Here, we attempt to provide a molecular perspective on prostate cancer racial disparities by gathering available information on these associated factors and discussing their potential significance in disproportionate incidence and clinical outcomes.

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Section: Role Of Aberrantly-activated Signaling Pathways In Prostamentioning

confidence: 99%

Racial disparities in prostate cancer a molecular perspective

et al. 2017

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“…The seeded cells were washed twice with PBS (1X) to remove spent media and serum. The lipofectamine 2000-siNA complexes were added to the cultures and incubated for 5 h and then media containing 20 % serum was added and transfected cells were further incubated for 20 h [23,24].…”

Section: Short-interfering Molecule Preparationmentioning

confidence: 99%

Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line

et al. 2015

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The diamine putrescine and polyamines, spermidine (triamine) and spermine (tetraamine) are small organic polycations that play an indispensable role in key cellular processes such as the regulation of growth, differentiation, and macromolecular functions. Elevated levels of polyamines (PAs) have been shown to be one of the major factors involved in carcinogenesis. In this study, specific silencing of the expression of three genes of PA biosynthesis pathway, ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (SAMDC), and spermidine synthase (SPDSYN) was achieved using RNA interference in MCF 7 breast cancer cell line. For optimizing the effective small interfering nucleic acid (siNA), three variants of ODC siNA [siRNA, locked nucleic acid (LNA)-modified siRNA, and siHybrid (RNA and DNA hybrid)] were used and a dose- and time-dependent study was conducted. The PA biosynthetic genes were targeted individually and in combination. RNAi-mediated reduction in the expression of PA biosynthesis genes resulted in distorted cell morphology, reduced cancer cell viability, and migration characteristic. The most promising results were observed with the combined treatment of siSPDSYN and siODC with 83 % cell growth inhibition. On analyzing the messenger RNA (mRNA) expression profile of the cell cycle and apoptosis-related genes, it was observed that RNAi against PA biosynthetic genes downregulated the expression of CDK8, CCNE2, CCNH, CCNT1, CCNT2, CCNF, PCNA, CCND1, and CDK2, and upregulated the expression of E2F4, BAX, FAS, TP53, CDKN1A, BAK1, CDKN1B, ATM, GRANB, and ATR genes when compared with control-transfected cells. These results suggest that the targeting polyamine biosynthesis through RNAi approach could be a promising strategy for breast cancer therapy and might be extended for therapy of other cancers.

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“…Several mechanisms have been proposed for chemoresistance of BC, which may involve both intrinsic and extrinsic factors [10, 11]. Tumor microenvironment (TME) is comprised of a heterogeneous mixture of many different cells that produce and secrete a number of growth factors and cytokines [12, 13]. Interestingly, a recent study suggested the existence of disparate TME in AA vs. CA breast tumors [13–15].…”

Section: Introductionmentioning

confidence: 99%

“…Tumor microenvironment (TME) is comprised of a heterogeneous mixture of many different cells that produce and secrete a number of growth factors and cytokines [12, 13]. Interestingly, a recent study suggested the existence of disparate TME in AA vs. CA breast tumors [13–15]. Emerging data have provided convincing evidence for an important role of TME in cancer chemoresistance, which involves both direct and indirect mechanisms [16, 17].…”

Section: Introductionmentioning

confidence: 99%

Resistin potentiates chemoresistance and stemness of breast cancer cells: Implications for racially disparate therapeutic outcomes

et al. 2017

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Breast cancer (BC) continues to be the most frequently diagnosed cancer in American women, which disproportionately affects women of African-American (AA) descent. Previously, we reported greater serum levels of resistin in AA BC patients relative to Caucasian-American (CA) patients, and established its role in growth and aggressiveness of breast tumor cells. Here we have investigated the role of resistin in BC-chemoresistance. MDA-MB-231 and MDA-MB-468 BC cells of CA and AA origin, respectively, were incubated with resistin prior to doxorubicin treatment. Our data suggest that resistin conferred chemoresistance to both BC cell lines; however, the effect on AA cells was more profound. Furthermore, the resistin-induced doxorubicin-resistance was shown to occur due to suppression of apoptosis. Resistin treatment also affected the stemness of BC cells, as suggested by reduced cell surface expression of CD24, induced expression of CD44 and ALDH1, and increased capability of cells to form mammospheres. Mechanistic studies revealed that resistin-induced chemoresistance, apoptosis and stemness of BC cells were mediated through STAT3 activation. Taken together, our findings provide novel insight into the role of resistin in BC biology, and strengthen its role in racially disparate clinical outcomes.

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Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation

Cited by 92 publications

References 54 publications

Racial disparities in prostate cancer a molecular perspective

Racial disparities in prostate cancer a molecular perspective

Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line

Resistin potentiates chemoresistance and stemness of breast cancer cells: Implications for racially disparate therapeutic outcomes

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