Overexpression of phosphoserine aminotransferase PSAT1 stimulates cell growth and increases chemoresistance of colon cancer cells

International audienceABSTRACT: BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer death throughout the world. In this work our aim was to study the role of the phosphoserine aminotransferase PSAT1 in colorectal cancer development. RESULTS: We first observed that PSAT1 is overexpressed in colon tumors. In addition, we showed that after drug treatment, PSAT1 expression level in hepatic metastases increased in non responder and decreased in responder patients. In experiments using human cell lines, we showed that ectopic PSAT1 overexpression in colon carcinoma SW480 cell line resulted in an increase in its growth rate and survival. In addition, SW480-PSAT1 cells presented a higher tumorigenic potential than SW480 control cells in xenografted mice. Moreover, the SW480-PSAT1 cell line was more resistant to oxaliplatin treatment than the non-transfected SW480 cell line. This resistance resulted from a decrease in the apoptotic response and in the mitotic catastrophes induced by the drug treatment. CONCLUSIONS: These results show that an enzyme playing a role in the L-serine biosynthesis could be implicated in colon cancer progression and chemoresistance and indicate that PSAT1 represents a new interesting target for CRC therapy

CULTURE DE PNEUMOCYTES FOETAUX DANS UN MILIEU CHIMIQUEMENT DEFINI

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A functional androgen receptor is not sufficient to allow estradiol to protect bone after gonadectomy in estradiol receptor–deficient mice

Although the role of estradiol in maintaining bone mass is well established, the relative contributions of the estradiol receptors ERα and ERβ and of the androgen receptor (AR) remain controversial. To determine the role of ERα-mediated, ERβ-mediated, and non–ER-mediated mechanisms in maintaining bone mass, gonadectomy and estradiol treatment were studied in ER-knockout mice. Estradiol treatment of ovariectomized ERαβ(–/–) mice failed to prevent bone loss, precluding significant effects of estradiol on bone through non–ER-signaling pathways. In contrast, estradiol prevented ovariectomy-induced bone loss in ERβ(–/–) mice, as in WT males and females, indicating that ERα is the major mediator of estradiol effects in bone. No response of bone to estradiol was detected in orchidectomized ERα(–/–) mice, suggesting estradiol cannot protect bone mass via the AR in vivo. In contrast to female ERαβ(–/–) and male ERα(–/–) mice, female ERα(–/–) mice were partially protected against ovariectomy-induced bone loss by estradiol, confirming that ERβ mediates estradiol effects in bone, but only in females and with a lower efficacy than ERα. We conclude that ERα is the main effector of estradiol’s protective function in bone in both male and female mice, and that, in its absence, AR is not sufficient to mediate this response