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All trans-retinoic acid (ATRA) induces re-differentiation of early transformed breast epithelial cells.

ABSTRACT: Retinoids have been used as potential chemotherapeutic or chemopreventive agents because of their differentiative, anti-proliferative, pro-apoptotic and antioxidant properties. We investigated the effect of all trans-retinoic acid (ATRA) at different stages of the neoplastic transformation using an in vitro model of breast cancer progression. This model was previously developed by treating the MCF-10F human normal breast epithelial cells with high dose of estradiol and consists of four cell lines which show a progressive neoplastic transformation: MCF-10F, normal stage; trMCF, transformed MCF-10F; bsMCF, invasive stage; and caMCF, tumorigenic stage. In 3D cultures, MCF-10F cells form tubules resembling the structures in the normal mammary gland. After treatment with estradiol, these cells formed tubules and spherical masses which are indicative of transformation. Cells that only formed spherical masses in collagen were isolated (trMCF clone 11) and treated with ATRA. After treatment with 10 or 1 µM ATRA, the trMCF clone 11 cells showed tubules in collagen; 10 and 43% of the structures were tubules in cells treated with 10 and 1 µM ATRA, respectively. Gene expression studies showed that 207 genes upregulated in transformed trMCF clone 11 cells were downregulated after 1 µM ATRA treatment to levels comparable to those found in the normal breast epithelial cells MCF-10F. Furthermore, 236 genes that were downregulated in trMCF clone 11 were upregulated after 1 µM ATRA treatment to similar levels shown in normal epithelial cells. These 443 genes defined a signature of the ATRA re-programming effect. Our results showed that 1 µM ATRA was able to re-differentiate transformed cells at early stages of the neoplastic process and antagonistically regulate breast cancer associated genes. The invasive and tumorigenic cells did not show any changes in morphology after ATRA treatment. These results suggest that ATRA could be used as a chemopreventive agent to inhibit the progression of premalignant lesions of the breast.

SUBMITTER: Arisi MF

PROVIDER: S-EPMC4063534 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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All trans-retinoic acid (ATRA) induces re-differentiation of early transformed breast epithelial cells.

Arisi Maria F MF Starker Rebecca A RA Addya Sankar S Huang Yong Y Fernandez Sandra V SV

International journal of oncology 20140321 6

Retinoids have been used as potential chemotherapeutic or chemopreventive agents because of their differentiative, anti-proliferative, pro-apoptotic and antioxidant properties. We investigated the effect of all trans-retinoic acid (ATRA) at different stages of the neoplastic transformation using an in vitro model of breast cancer progression. This model was previously developed by treating the MCF-10F human normal breast epithelial cells with high dose of estradiol and consists of four cell line ...[more]

PMID: 24676586

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Project description:Retinoids have been used as potential chemotherapeutic or chemo-preventive agents because of their differentiation, anti-proliferative, pro-apoptotic, and anti-oxidant effects. We investigated the effect of all trans- retinoic acid (ATRA) at different stages of the neoplastic transformation using an in vitro model of breast cancer progression. This model was previously developed by treating the human normal-like breast epithelial MCF-10F cells with high dose of estradiol and consist of five cell lines which shown a progressive neoplastic transformation: MCF-10F (normal stage), trMCF (premalignant stage), bsMCF (invasive stage) and caMCF (tumorigenic stage). In 3D-cultures, MCF-10F cells form tubules resembling the normal mammary gland although after treatment with high doses of estradiol, trMCF cells, formed tubules and, spherical masses which are an indication of cell transformation. By ring cloning, trMCF clone 11 which only formed spherical masses in collagen was isolated. Our results showed that the early transformed trMCF clone 11 cells shown a reduction of spherical masses and increased of tubules in collagen after being treated with 10-5M (10µM) and 10-6M (1µM) ATRA; the number of tubules was higher in cells treated with 10-6M ATRA (43% vs. 10% tubules). The invasive bsMCF and tumorigenic caMCF cells did not shown any changes in morphology after ATRA treatment. Analysis of expression studies in early transformed cells treated with 10-6M ATRA showed that 271 probes upregulated in trMCF clone 11 cells were downregulated after ATRA treatment and, 316 probes that were downregulated were upregulated after ATRA treatment in these cells to similar levels than the normal breast epithelial cells MCF-10F. These genes were involved in the aryl hydrocarbon receptor signaling, RAR Activation, xenobiotic metabolisms signaling, molecular mechanisms of cancer and cell morphology. Our results shown that ATRA was able to re-differentiate transformed cells at early stages of the neoplastic process suggesting that ATRA could potentially be used to inhibit the progression of premalignant lesions of the breast such as ductal carcinoma in situ (DCIS). We investigated the effect of all trans- retinoic acid (ATRA) at different stages of the neoplastic transformation using an in vitro model of breast cancer progression. This model was previously developed by treating the human normal-like breast epithelial MCF-10F cells with high dose of estradiol and consist of five cell lines which shown a progressive neoplastic transformation: MCF-10F (normal stage), trMCF (premalignant stage), bsMCF (invasive stage) and caMCF (tumorigenic stage).

Project description:Retinoids have been used as potential chemotherapeutic or chemo-preventive agents because of their differentiation, anti-proliferative, pro-apoptotic, and anti-oxidant effects. We investigated the effect of all trans- retinoic acid (ATRA) at different stages of the neoplastic transformation using an in vitro model of breast cancer progression. This model was previously developed by treating the human normal-like breast epithelial MCF-10F cells with high dose of estradiol and consist of five cell lines which shown a progressive neoplastic transformation: MCF-10F (normal stage), trMCF (premalignant stage), bsMCF (invasive stage) and caMCF (tumorigenic stage). In 3D-cultures, MCF-10F cells form tubules resembling the normal mammary gland although after treatment with high doses of estradiol, trMCF cells, formed tubules and, spherical masses which are an indication of cell transformation. By ring cloning, trMCF clone 11 which only formed spherical masses in collagen was isolated. Our results showed that the early transformed trMCF clone 11 cells shown a reduction of spherical masses and increased of tubules in collagen after being treated with 10-5M (10M-BM-5M) and 10-6M (1M-BM-5M) ATRA; the number of tubules was higher in cells treated with 10-6M ATRA (43% vs. 10% tubules). The invasive bsMCF and tumorigenic caMCF cells did not shown any changes in morphology after ATRA treatment. Analysis of expression studies in early transformed cells treated with 10-6M ATRA showed that 271 probes upregulated in trMCF clone 11 cells were downregulated after ATRA treatment and, 316 probes that were downregulated were upregulated after ATRA treatment in these cells to similar levels than the normal breast epithelial cells MCF-10F. These genes were involved in the aryl hydrocarbon receptor signaling, RAR Activation, xenobiotic metabolisms signaling, molecular mechanisms of cancer and cell morphology. Our results shown that ATRA was able to re-differentiate transformed cells at early stages of the neoplastic process suggesting that ATRA could potentially be used to inhibit the progression of premalignant lesions of the breast such as ductal carcinoma in situ (DCIS). We investigated the effect of all trans- retinoic acid (ATRA) at different stages of the neoplastic transformation using an in vitro model of breast cancer progression. This model was previously developed by treating the human normal-like breast epithelial MCF-10F cells with high dose of estradiol and consist of five cell lines which shown a progressive neoplastic transformation: MCF-10F (normal stage), trMCF (premalignant stage), bsMCF (invasive stage) and caMCF (tumorigenic stage).

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All trans-retinoic acid (ATRA) induces re-differentiation of early transformed breast epithelial cells.

Publications

All trans-retinoic acid (ATRA) induces re-differentiation of early transformed breast epithelial cells.

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