Estrogen withdrawal, increased breast cancer risk and the KRAS-variant

McVeigh, Terri P; Jung, Song-Yi; Kerin, Michael J.; Salzman, David W.; Nallur, Sunitha; Nemec, Antonio A; Dookwah, Michelle; Sadofsky, Jackie; Paranjape, Trupti; Kelly, Olivia G.; Chan, Eugenia L.; Miller, Nicola; Sweeney, Karl; Zelterman, Daniel; Sweasy, Joann B.; Pilarski, Robert; Telesca, Donatello; Slack, Frank J.; Weidhaas, Joanne B.

doi:10.1080/15384101.2015.1041694

Cited by 13 publications

(15 citation statements)

References 39 publications

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“…This gene mainly functions in signaling pathways involving membrane receptors and cAMP. KRAS has the strongest influence on malignant cancer in the RAS family (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

miR‑202 acts as a potential tumor suppressor in breast cancer

et al. 2018

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Abstract. Breast cancer affects ~10% of women worldwide and is responsible for ~12% of all cancer-associated mortalities. Breast cancer is more prone to metastasis compared with other types of cancer. Up to 5% of patients with breast cancer present with incurable metastasis and an additional 10-15% of patients develop metastases within 3 years of their initial diagnosis. MicroRNAs (miRNAs) are short RNAs, 21-25 nucleotides in length, that have been shown to significantly affect gene expression. In total >2,000 miRNAs have been identified and specific miRNAs have been revealed to be associated with cancer. In the present study, we observed that the majority of breast cancer specimens collected expressed low levels of miR-202 compared with adjacent tissues and normal cell lines. Mechanistic investigations identified KRAS as a potential target gene of miR-202 and it was demonstrated that miR-202 exerted its tumor-suppressive effects by regulating the expression of KRAS in breast cancer cells. Functional assays revealed that miR-202 significantly reduced cell proliferation, migration and invasion in vitro. In summary, these results indicate the function of miR-202 in breast cancer progression and suggest that its use within breast cancer therapy is promising. IntroductionBreast cancer is one of the most common malignant tumors in women. In many areas, breast cancer is the most common malignancy in females. In China, the incidence of breast cancer is increasing annually. Because the development and progression of breast cancer are complex processes involving many genes, the underlying mechanism of breast cancer remains unclear (1,2).Single-stranded RNAs consisting of 19 to 25 nucleotides are known as microRNAs (miRNAs). These RNAs are regulatory molecules that modulate the expression of functional genes, play an important role in many biological processes, and are expressed in a tissue-and time-specific manner. miRNAs regulate gene expression at the post-transcriptional level mainly via completely complementary or partially complementary binding to the 3' UTR of the target gene, resulting in degradation or translational repression of the target gene (2-4). Studies have shown that a variety of miRNAs are involved in malignant transformation processes, such as malignant proliferation, metastasis and recurrence, and apoptosis inhibition. Studies have reported that miRNA inhibitors can reduce the high miR-21 expression in breast cancer cells, inhibiting proliferation and migration; that miR-373 can promote the metastasis of breast cancer cells; that miR-520 plays a role in promoting the development of breast cancer; and that miR-126 and miR-335 are able to inhibit breast cancer to a certain extent (5-7). Recent studies have demonstrated that miR-202 is associated with several types of cancer, miR-202 has a lower expression in several of cancers, and however, the expression and function of miR-202 have not been investigated in breast cancer (8).KRAS belongs to the RAS family; it is located on the short arm of chromosome 1...

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“…This gene mainly functions in signaling pathways involving membrane receptors and cAMP. KRAS has the strongest influence on malignant cancer in the RAS family (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

miR‑202 acts as a potential tumor suppressor in breast cancer

et al. 2018

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“…In a recent study from Ovarian Cancer Association Consortium and colleagues with performed rs61764370 genotyping for 140,012 women the authors reported no association of rs61764370 with risk of ovarian or breast cancer nor with clinical outcome [5]. Whereas McVeigh and colleagues described the KRAS variant as significant marker, which in combination with estrogen withdrawal increases breast cancer risk and predicts aggressive tumor biology [6].…”

Section: S I N G L E N U C L E O T I D E P O L Y M O R P H I S M Rs61mentioning

confidence: 99%

IMPACT OF KRAS VARIANT rs61764370 ON BREAST CANCER MORBIDITY

Ustinova¹,

Daneberga²,

Berzina³

et al. 2015

Exp. Onc.

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Low-penetrance gene variants and their combinations are topical study objects in breast cancer pathogenesis. Single nucleotide polymorphism rs61764370, localized in 3 UTR of KRAS gene, plays an important role in the development and progression of several cancers. The aim of our study was to determine the KRAS variant impact on breast cancer morbidity. Patients and Methods: 2214 patients diagnosed with breast cancer and 861 healthy controls were screened for KRAS variant by RFLP method. Available clinical data were collected and processed using statistical analysis methods. Results of present study suggest the KRAS variant impact on breast cancer development risk in premenopausal women, but it has no effect on breast cancer prognosis. We did not observe any KRAS variant effect on breast cancer patient 10-year disease-specific survival rates.

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“…5 This combination of clinical observations led McVeigh and colleagues to investigate how estrogen might impact breast cancer risk and tumor biology for individuals with the KRAS-variant allele. 6 In their study, 1712…”

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confidence: 92%