Yayun Liang,1,2,* Sandy Goyette,1,2,* Salman M Hyder1,2
1Department of Biomedical Sciences, 2Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA
*These authors contributed equally to this work
Abstract: Clinical trials and studies have shown that postmenopausal women undergoing combination hormone replacement therapy containing estrogen and progestin have an increased risk of breast cancer compared with women taking estrogen or placebo alone. Using animal models, we have previously shown that synthetic progestins, including medroxyprogesterone acetate (MPA), which is widely used clinically, accelerate breast cancer tumor growth and promote metastasis. Furthermore, we have found that MPA elevates CD44 protein expression and aldehyde dehydrogenase (ALDH) activity, two markers of cancer stem cells (CSCs), and increases mammosphere formation, another hallmark of stem cells, in hormone-dependent T47-D human breast cancer cells. Herein, we show that RO 48-8071 (RO), an inhibitor of cholesterol synthesis, reduced MPA-induced CD44 protein expression in two hormone-dependent human breast cancer cell lines, T47-D and BT-474. Because we have previously shown that MPA induction of CD44 is progesterone receptor (PR) dependent, we examined ROs effects on PR protein and mRNA expressions in T47-D cells. PR mRNA levels remained unchanged after RO treatment; however, RO significantly reduced the protein expression of both PR receptor isoforms, PR-A and PR-B. Using the proteasome inhibitor MG-132, we demonstrated that RO decreases PR protein expression in T47-D cells via the proteasomal degradation pathway. Importantly, treatment of T47-D cells with RO abolished MPA-induced mammosphere formation. Based on our observations, we contend that RO may represent a novel means of preventing MPA-induced CSC expansion. RO could be used clinically to both treat and prevent hormone-dependent breast cancers, which represent the majority of human breast cancers. RO may also have clinical utility in reducing resistance to antihormone therapy.
Keywords: breast cancer, cholesterol biosynthesis inhibitor, RO 48-8071, medroxyprogesterone acetate, cancer stem cells, CD44
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.
Original post:
Cholesterol biosynthesis inhibitor RO 48-8071 reduces progesterone receptor expression and inhibits progestin ... - Dove Medical Press
- Bio Identical Hormone replacement therapy "alternative medicine" OMT - June 1st, 2010 [June 1st, 2010]
- Healthbeat - Hormone Replacement Therapy - August 5th, 2010 [August 5th, 2010]
- Does Hormone Replacement Therapy increase breast cancer risks? - August 11th, 2010 [August 11th, 2010]
- Hormone replacement therapy increases risk of cancer - October 20th, 2010 [October 20th, 2010]
- Hormone Replacement Therapy Risky For Women - October 20th, 2010 [October 20th, 2010]
- Can Hormone Replacement Therapy Lead To Breast Cancer? - January 31st, 2011 [January 31st, 2011]
- Women Turning To Holistic Hormone Replacement Therapy - February 18th, 2011 [February 18th, 2011]
- Is Hormone Replacement Therapy Dangerous? - March 17th, 2011 [March 17th, 2011]
- Hormone Replacement Therapy Complications - May 8th, 2011 [May 8th, 2011]
- Hormone Replacement Therapy - May 10th, 2011 [May 10th, 2011]
- The New Growth Hormone Replacement Therapy - John Crisler, DO - May 13th, 2011 [May 13th, 2011]
- Suzanne Somers on hormone therapy for menopause, part 2 of 6 - May 20th, 2011 [May 20th, 2011]
- Symptoms of Menopause (Menopause #2) - May 20th, 2011 [May 20th, 2011]
- How to Relieve Menopause Symptoms : Hormonal Replacement Therapy for Menopause - May 20th, 2011 [May 20th, 2011]
- HRT - Hormone Replacement Therapy - May 20th, 2011 [May 20th, 2011]
- What is hormone replacement therapy? - May 20th, 2011 [May 20th, 2011]
- Hormone Replacement Therapy and Breast Cancer - May 20th, 2011 [May 20th, 2011]
- Natural Treatments Instead of Hormone Replacement Therapy - May 20th, 2011 [May 20th, 2011]
- Suzanne Somers on hormone therapy for menopause, part 1 of 6 - May 23rd, 2011 [May 23rd, 2011]
- Hormone Replacement Therapy for post-menopausal women - June 19th, 2011 [June 19th, 2011]
- Joe Rogan talking about hormone replacement therapy 6-14-2011 - June 25th, 2011 [June 25th, 2011]
- Hormone Replacement Therapy and Weight - June 25th, 2011 [June 25th, 2011]
- HRC Hormone Replacement Therapy - June 25th, 2011 [June 25th, 2011]
- Study Hormone Replacement Therapy Increases Breast Cancer Risk - kdka.com - June 25th, 2011 [June 25th, 2011]
- 020 - Neo Hormones - July 1st, 2011 [July 1st, 2011]
- Making Sense of Hormone Replacement Therapy - July 28th, 2011 [July 28th, 2011]
- HRT MTF Transition Report Week 10 - July 29th, 2011 [July 29th, 2011]
- Hormone Replacement - Part 2 - July 30th, 2011 [July 30th, 2011]
- Hormone Replacement - Part 1 - July 30th, 2011 [July 30th, 2011]
- Goldie Lookin Chain - HRT - August 9th, 2011 [August 9th, 2011]
- Natural Hormone Replacement Therapy - September 23rd, 2011 [September 23rd, 2011]
- Testosterone Replacement Therapy (TRT): Optimizing Clinical Outcomes - Michael Aziz, MD - September 24th, 2011 [September 24th, 2011]
- Thyroid Replacement Therapy - Ronald Rothenberg, MD - September 24th, 2011 [September 24th, 2011]
- Dr. Ralph Turner discusses Hormone Replacement Therapy. - September 24th, 2011 [September 24th, 2011]
- 1 year on HRT - September 24th, 2011 [September 24th, 2011]
- The Wiley Protocol - September 24th, 2011 [September 24th, 2011]
- My Journal with Low Testosterone TRT Replacement Therapy - September 24th, 2011 [September 24th, 2011]
- 12 years of HRT: My Transition in photos - September 24th, 2011 [September 24th, 2011]
- Dr. Steven Jepson talks about Bio-identical Hormone Replacment Therapy - September 25th, 2011 [September 25th, 2011]
- Estradiol Valerate Injection HRT (Part 3)of(3) - September 25th, 2011 [September 25th, 2011]
- Study: Post-Menopausal Hormone Therapy Increases Cancer Risk - September 25th, 2011 [September 25th, 2011]
- Bio-identical Hormone Replacement (anti-aging) Therapy - Westchase, Tampa, Florida - September 25th, 2011 [September 25th, 2011]
- natural hormone replacement - September 28th, 2011 [September 28th, 2011]
- 6 Month Hormone Effects (before and after) - September 28th, 2011 [September 28th, 2011]
- Jeff Life, MD - Cenegenics, Hormone Replacement Therapy - September 29th, 2011 [September 29th, 2011]
- Huge - September 30th, 2011 [September 30th, 2011]
- Transsexual hormones,Intramuscular injection, Progynon Depot,Estradiol - October 2nd, 2011 [October 2nd, 2011]
- Dr Whiting on Menopause and the Dangers of HRT - October 12th, 2011 [October 12th, 2011]
- Ahuviya Harel (ADF-Fuensalida) to Start Hormone Replacement Therapy - October 13th, 2011 [October 13th, 2011]
- Clomid Defined - Video - October 14th, 2011 [October 14th, 2011]
- Thyroid Hormone Replacement Therapy - Dr. Denis Rebic - Video - October 14th, 2011 [October 14th, 2011]
- Hormone Replacement Therapy - Video - October 14th, 2011 [October 14th, 2011]
- Dr. Pamela Smith - Bio-Identical Hormone Replacement - Video - October 15th, 2011 [October 15th, 2011]
- Jasper Carrott - Traffic - October 22nd, 2011 [October 22nd, 2011]
- VIDEO: Breast Cancer, Hormone Replacement Therapy Connection - Video - October 24th, 2011 [October 24th, 2011]
- Menopause and Hormone Replacement Therapy with Dr. Sulak - Video - October 24th, 2011 [October 24th, 2011]
- Menopause - October 24th, 2011 [October 24th, 2011]
- bio identical hormone replacement therapy raleigh durcham chaepl hill north carolina - Video - October 24th, 2011 [October 24th, 2011]
- Endocrine Related Hair Loss, Can Hormone Replacement Therapy Help Treat This? Friedman - Video - October 24th, 2011 [October 24th, 2011]
- Dr. Navarro Discusses Bio Identical Hormone Replacement Therapy - Video - October 24th, 2011 [October 24th, 2011]
- Hormone Replacement Therapy by the Book - Eldred Taylor, MD - Video - October 24th, 2011 [October 24th, 2011]
- Sangeeta Pati, MD, FACOG, discusses Hormone Replacement - Video - October 24th, 2011 [October 24th, 2011]
- Active Center's Dr. Gross Discusses Bio-Identical Hormone Replacement Therapy on NEWS 12 NJ - Video - October 28th, 2011 [October 28th, 2011]
- DALLAS ANTI-AGING MEDICINE BIO-IDENTICAL HORMONE THERAPY - Video - October 29th, 2011 [October 29th, 2011]
- Hormone Replacement Therapy and Menopause in Women - Video - November 8th, 2011 [November 8th, 2011]
- Amberen - Natural HRT Alternative Commercial - Video - November 9th, 2011 [November 9th, 2011]
- The Dangers of HRT - Video - November 11th, 2011 [November 11th, 2011]
- The Benefits and Risks of Male Hormone Replacement Therapy - Video - November 16th, 2011 [November 16th, 2011]
- Natural Menopause Treatment - Herbal HRT Alternative - Video - November 23rd, 2011 [November 23rd, 2011]
- Dr. Ian Thorneycroft - Hormone Replacement Therapy - Video - November 24th, 2011 [November 24th, 2011]
- Sarah,MTF Transgender 3months HRT - Video - November 24th, 2011 [November 24th, 2011]
- 26. ftm 1 month on t - Video - November 24th, 2011 [November 24th, 2011]
- Dr. Quint Jardine - Hormone Replacement Therapy with Pellets - Video - November 24th, 2011 [November 24th, 2011]
- 6 Month Changes MTF HRT - Video - November 24th, 2011 [November 24th, 2011]
- Medical Mondays: Will hormone replacement therapy increase my risk of breast cancer? - Video - December 6th, 2011 [December 6th, 2011]
- HRT EXPERIENCES NOT ALL GOOD - Video - December 8th, 2011 [December 8th, 2011]
- Sarah, MTF transgender 9 months HRT - Video - December 9th, 2011 [December 9th, 2011]
- Full: Effect of Testosterone Replacement Therapy on Prostate Tissue in Men with Late-Onset Hypogonadism (Dramatic Health) - Video - December 10th, 2011 [December 10th, 2011]
- Suzanne Somers on hormone therapy for menopause, part 3 of 6 - Video - December 11th, 2011 [December 11th, 2011]
- 1 Year HRT MTF Transition - Video - December 12th, 2011 [December 12th, 2011]